Epitranscriptomic regulation of HIF-1: bidirectional regulatory pathways
Molecular Medicine,
Год журнала:
2025,
Номер
31(1)
Опубликована: Март 18, 2025
Abstract
Background
Epitranscriptomics,
the
study
of
RNA
modifications
such
as
N
6
-methyladenosine
(m
A),
provides
a
novel
layer
gene
expression
regulation
with
implications
for
numerous
biological
processes,
including
cellular
adaptation
to
hypoxia.
Hypoxia-inducible
factor-1
(HIF-1),
master
regulator
response
low
oxygen,
plays
critical
role
in
adaptive
and
pathological
cancer,
ischemic
heart
disease,
metabolic
disorders.
Recent
discoveries
accent
dynamic
interplay
between
m
A
HIF-1
signaling,
revealing
complex
bidirectional
regulatory
network.
While
roles
other
remain
largely
unexplored,
emerging
evidence
suggests
their
potential
significance.
Main
body
This
review
examines
reciprocal
epitranscriptomic
machinery,
writers,
readers,
erasers.
modulates
key
components,
while
its
own
mRNA
is
regulated
by
modifications,
positioning
both
target
this
system.
interaction
enhances
our
understanding
hypoxic
responses
opens
avenues
clinical
applications
treating
conditions
like
cancer
disease.
Promising
progress
has
been
made
developing
selective
inhibitors
targeting
A-HIF-1
axis.
However,
challenges
off-target
effects
complexity
modification
dynamics
significant
barriers
translation.
Conclusion
The
intricate
highlights
epitranscriptomics
hypoxia-driven
processes.
Further
research
into
these
networks
could
drive
therapeutic
innovation
hypoxia-related
conditions.
Overcoming
specificity
will
be
essential
realizing
therapies.
Язык: Английский
Mitochondrial Bioenergetics in Physiology
Acta Physiologica,
Год журнала:
2025,
Номер
241(6)
Опубликована: Май 19, 2025
Язык: Английский
Identification of autophagy-related genes in intestinal ischemia-reperfusion injury and their role in immune infiltration
Frontiers in Physiology,
Год журнала:
2025,
Номер
16
Опубликована: Май 26, 2025
Background
Intestinal
ischemia-reperfusion
(II/R)
injury
is
a
serious
condition
characterized
by
high
morbidity
and
mortality
rates.
Research
has
shown
that
II/R
closely
linked
to
autophagy
immune
dysregulation.
This
study
aims
investigate
the
potential
correlations
between
autophagy-related
genes
infiltrating
cells
in
injury.
Methods
GSE96733,
GSE37013,
were
obtained
from
Gene
Expression
Omnibus
(GEO)
Human
Autophagy
Database,
respectively.
Subsequently,
biological
functions
of
differentially
expressed
(DEGs)
explored
through
DEGs
analysis,
Kyoto
Encyclopedia
Genes
Genomes
(KEGG)
Ontology
(GO)
analysis.
Using
R
software,
human
converted
their
mouse
homologous
(ARGs).
The
then
intersected
with
ARGs
obtain
(DEARGs).
To
identify
hub
genes,
protein-protein
interaction
(PPI)
network
Lasso
regression,
random
forest
methods
employed.
A
nomogram
model
was
constructed
assess
its
diagnostic
value.
Following
this,
infiltration
analysis
performed
evaluate
correlation
Hub
cell
infiltration.
Additionally,
gene-related
constructed,
drugs
targeting
for
treatment
predicted.
Finally,
expression
levels
validated
dataset
verification
quantitative
real-time
polymerase
chain
reaction
(qRT-PCR).
Results
Our
identified
11
DEARGs.
Among
these,
5
DEARGs
(Myc,
Hif1a,
Zfyve1,
Sqstm1,
Gabarapl1)
as
genes.
demonstrated
excellent
Immune
indicated
these
are
associated
dendritic
M2.Macrophage.
Furthermore,
regulatory
illustrated
complex
relationship
microRNAs
(miRNAs)
trigonelline
niacinamide
predicted
therapeutic
agents
In
both
validation
qRT-PCR
validation,
four
showed
consistency
results
bioinformatics
Conclusion
Myc,
Gabarapl1
have
been
These
may
represent
targets
Язык: Английский
Unveiling the proteome of the fasting heart: Insights into HIF-1 pathway regulation
Frontiers in Physiology,
Год журнала:
2024,
Номер
15
Опубликована: Окт. 14, 2024
Fasting
is
a
common
dietary
intervention
known
for
its
protective
effects
against
metabolic
and
cardiovascular
diseases.
While
are
mostly
systemic,
understanding
tissue-specific
changes
in
the
heart
crucial
identification
of
mechanisms
underlying
fasting-induced
cardioprotection.
In
this
study,
we
performed
proteomic
analysis
fasting
attempted
to
clarify
molecular
basis
Our
investigation
identified
total
4,652
proteins,
with
127
exhibiting
downregulation
118
showing
upregulation
after
fasting.
Annotation
highlighted
significant
processes
such
as
lipid
metabolism,
peroxisome
pathway,
reactive
oxygen
species
metabolism.
Notably,
HIF-1
signaling
pathway
emerged
one
focal
points,
various
targets
differential
responses
Further
experiments
demonstrated
HIF-1α
at
both
transcript
protein
levels.
Intriguingly,
while
gene
expression
Egln3
decreased,
product
PHD3
remained
unaffected
by
The
unchanged
levels
pro-inflammatory
cytokines
indicated
that
observed
reduction
Hif1a
did
not
stem
from
decrease
basal
inflammation.
These
findings
underscore
complex
regulation
well-established
cardioprotective
within
during
3-day
Язык: Английский
Sodium Orthovanadate Mitigates Nonalcoholic Fatty Liver Disease by Enhancing Autophagy
Biological and Pharmaceutical Bulletin,
Год журнала:
2024,
Номер
47(10), С. 1786 - 1795
Опубликована: Окт. 30, 2024
Sodium
orthovanadate
(SOV)
has
been
investigated
in
recent
research
for
its
therapeutic
efficacy
treating
metabolic
disorders.
Considering
the
rising
prevalence
of
non-alcoholic
fatty
liver
disease
(NAFLD),
effects
SOV
on
NAFLD
remain
to
be
further
investigated.
The
aim
this
study
was
investigate
role
and
mechanism
NAFLD.
Two
mouse
models
were
established
by
induction
with
high
fat
diet
(HFD)
Western
supplemented
sugar
drinking
water
(WDS),
respectively.
We
searched
downstream
molecules
RNA
sequencing,
followed
rescue
experiments
an
autophagy
inhibitor
(3-MA)
HepG2
cells
as
well
animal
models.
results
showed
that
HFD
WDS-induced
models,
significantly
reduced
body
weight,
inhibited
lipid
deposition,
lowered
serum
triglyceride
cholesterol
levels.
Then
sequencing
RT-PCR
found
effect
might
related
activation
coregulated
hypoxia-inducible
factor
1
autophagy-related
gene
5.
protective
SOV-activated
blocked
3-MA,
leading
restoration
deposition
vitro
vivo.
conclude
could
activate
cell
autophagy,
thereby
improving
metabolism
during
course
Our
findings
revealed
potential
controlling
Язык: Английский
How to visualize high‐dimensional data
Acta Physiologica,
Год журнала:
2024,
Номер
240(10)
Опубликована: Авг. 19, 2024
Recently,
a
colleague
asked
after
lecture
about
fancy
diagram
where
the
axis
designation
was
not
clear
to
him
and
discussion
that
raised
few
interesting
thoughts
specific
matter.
Physiological
knowledge
is
often
taught
at
university
seminars
in
textbooks
with
help
of
diagrams.
A
very
important
first
step
when
discussing
diagrams
clarify
which
physical,
physiological
variable
what
scale
unit
represented
on
axis.
Examples
typical
classical
low
dimensional
physiology
publications
Acta
Physiologica
might
be
blood
pressure
over
time,1
infarct
size
as
percentage
Left
ventricular
mass
depending
genotype2
or
urine
excretion
volume
per
time
diet.3
Not
knowing
axes
diagrams,
they
well
"just"
pieces
modern
art.
We
strongly
believe
graphical
representation
complex
data—for
example,
diagrams—is
essential
communicating
them.
However,
for
types
understanding
interpretation
their
content
more
complex,
requires
explanation
than
Specifically,
we
refer
high-dimensional
data,
have,
recent
years,
played
an
increasing
role
new
understandings
processes.
To
visualize
data
reduction
dimensionality
applied.
simple
example
black/white
photograph
colorful
moving
three
object.
The
snapshot
"eliminated"
dimension
optical
projection
plane
camera
eliminated
one
space
gray
values
just
reduced
spectral
information
intensity
value
photograph.
Although
does
represent
compete
"dataset"
it
gives
us
most
cases
good
impression
situation
captured
by
photographer.
Times
have
changed.
describe
"amount"
obtained
study
1960s
physiologist
referred
length
paper
plots
curved
measurements
he
analyzing
particular
study.
Compared
amount
back
then
are
nowadays
faced
completely
situation.
With
development
technology
handle
huge
today.
For
studies
single
RNAseq
scientists
thousands
expression
genes
each
cells
multiple
experimental
points
possibly
interventions.
Obviously
you
cannot
produce
meaningful
plot
dimensions.
In
order
make
sense
out
hugely
researches
can
employ
methods
dimensionality.
One
would
so
called
principal
component
analysis
(PCA).
This
linear
method
projects
onto
coordinate
system
(principal
components)
directions
maximum
variance.
Without
diving
too
deep
into
mathematics,
this
done
calculating
eigenvectors
matrix.
It
turned
PCA
its
transformation
sufficient
above
described
case.
Here
statistical
approaches
nonlinear
been
developed.
t-Distributed
Stochastic
Neighbor
Embedding
(t-SNE)
method4
later
kind
improved
version
Uniform
Manifold
Approximation
Projection
(UMAP).5
Both
techniques
used
visualizing
data.
features
regarding
that,
unlike
well-defined
physical
quantities
such
voltage
axes,
t-SNE
UMAP
abstract
interpretations.
positions
reflect
(probability)-relationships
between
individual
original
space,
whereby
find
clustered
clouds.
clouds
close
together
considered
similar
closely
related
space.
When
comparing
UMAP,
differentiate
local
structure
global
diagram.
preserves
is,
diagram,
cluster
point
higher
However
accurately
preserved
method.
main
comes
play.
aims
preserve
both
structures
effectively
Therefore,
suitable
feature
topology
relevant
interpretation.
case
lineage
stem
cell
maturation.
illustrate
performance
generated
datasets
them
all
tree
(Figure
2).
also
possible
perform
analysis.6
widely
field
neurophysiology,7
immunology,8
cancer9,
10
infectious
diseases
like
COVID-19.11
Taken
together,
applied
far.
Clusters
revealed
usage
literature
has
growing
steadily
scientific
since
publication
1).
meaning
straightforward
compared
traditional
physiology,
spread
showing
variance
what?
mapping
while
scales
neighboring
relationships
aimed
preserve.
better
preserving
scales;
however,
cautious
distances
clusters
due
transformations.
There
efforts
further
improve
those
methods.12
will
see
whether
resonance
application
community.
come
beginning:
please
remember
take
second
explain
your
show
presentation.
As
rather
interdisciplinary
develop
rapidly,
likely
part
audience
otherwise
admiring
beautiful
graphic
Generation
displayed
Figure
2:
set
(upper
row)
array
200
5
mean
1,
2,
3,
4,
0.8
standard
deviation.
(middle
accordingly
means
8,
16
deviation
0.5
mean.
third
(lower
10,
100,
1000,
000
deviations
equal
Data
graphs
were
using
R
software
4.4.0
(2024-04-24)
library
RtSNE,13
ggplot2,
umap14
default
parameters.
RM
did
statistics
pubmed
occurences.
RS
anaysis
figure
2.
wrote
initial
text.
authors
edited
final
manuscript.
project
these
results
based
funded
FreeState
Thuringia
under
number
2018
IZN0002
(Thimedop)
co-financed
funds
from
European
Union
within
framework
Regional
Development
Fund
(EFRE).
Another
Carl
Zeiss
Foundation.
None.
Язык: Английский
Andrographolide Attenuates Myocardial Ischemia–Reperfusion Injury in Mice by Up-Regulating PPAR-α
Inflammation,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 25, 2024
Язык: Английский
Mitochondrial Peroxiredoxins and Monoamine Oxidase-A: Dynamic Regulators of ROS Signaling in Cardioprotection
Physiological Research,
Год журнала:
2024,
Номер
unknown, С. 887 - 900
Опубликована: Дек. 31, 2024
An
excessive
increase
in
reactive
oxygen
species
(ROS)
levels
is
one
of
the
main
causes
mitochondrial
dysfunction.
However,
when
ROS
are
maintained
balance
with
antioxidant
mechanisms,
fulfill
role
signaling
molecules
and
modulate
various
physiological
processes.
Recent
advances
bioenergetics
research
have
revealed
a
significant
interplay
between
peroxiredoxins
(PRDXs)
monoamine
oxidase-A
(MAO-A)
regulating
levels.
Both
proteins
associated
hydrogen
peroxide
(H2O2),
MAO-A
as
producer
PRDXs
primary
scavengers
H2O2.
This
review
focuses
on
currently
available
knowledge
function
these
their
interaction,
highlighting
importance
oxidative
damage,
apoptosis,
metabolic
adaptation
heart.
not
only
scavenge
excess
H2O2,
but
also
act
regulatory
proteins,
play
an
active
redox
signaling,
maintain
membrane
integrity.
Overexpression
increased
leading
to
dysfunction
subsequent
progression
cardiovascular
diseases
(CVD),
including
ischemia/reperfusion
injury
heart
failure.
Considering
central
damage
pathogenesis
many
CVD,
targeting
activation
inhibition
may
offer
new
therapeutic
strategies
aimed
at
improving
cardiac
under
conditions
pathological
load
related
damage.
Keywords:
Mitochondria,
Peroxiredoxin,
Monoamine
oxidase-A,
Reactive
species,
Cardioprotective
signaling.
Язык: Английский