International Journal of Molecular Sciences,
Год журнала:
2020,
Номер
22(1), С. 294 - 294
Опубликована: Дек. 30, 2020
The
heme
oxygenase
(HO)
system
involves
three
isoforms
of
this
enzyme,
HO-1,
HO-2,
and
HO-3.
them
display
the
same
catalytic
activity,
oxidating
group
to
produce
biliverdin,
ferrous
iron,
carbon
monoxide
(CO).
HO-1
is
isoform
most
widely
studied
in
proinflammatory
diseases
because
treatments
that
overexpress
enzyme
promote
generation
anti-inflammatory
products.
However,
neonatal
jaundice
(hyperbilirubinemia)
derived
from
HO
overexpression
led
development
inhibitors,
such
as
those
based
on
metaloproto-
meso-porphyrins
inhibitors
with
competitive
activity.
Further,
non-competitive
have
also
been
identified,
synthetic
natural
imidazole-dioxolane-based,
small
molecules,
regulation
pathway,
genetic
engineering
using
iRNA
or
CRISPR
cas9.
Despite
applications
being
related
metabolic
diseases,
beneficial
effects
these
molecules
immune-mediated
emerged.
Different
medical
implications,
including
cancer,
Alzheimer´s
disease,
infections,
are
discussed
article
how
selective
inhibition
may
contribute
treatment
ailments.
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Янв. 2, 2025
Nasopharyngeal
carcinoma
(NPC)
presents
significant
treatment
challenges
due
to
its
complex
etiology
and
late-stage
diagnosis.
The
traditional
Chinese
medicine
Selaginella
doederleinii
Hieron
(S.
doederleinii)
has
shown
potentiality
in
NPC
multi-target,
multi-pathway
anti-cancer
mechanisms.
First,
we
identified
related
target
genes
from
databases
like
GeneCards,
OMIM,
DisGeNET,
performed
WGCNA
analysis
on
the
GSE53819
dataset
identify
several
important
gene
modules
NPC.
Active
components
their
targets
S.
were
screened
TCMSP
other
databases,
identifying
32
overlapping
genes.
Gene
Ontology
(GO)
Kyoto
Encyclopedia
of
Genes
Genomes
(KEGG)
pathway
revealed
that
these
are
primarily
involved
critical
biological
processes
protein
phosphorylation
cell
cycle
regulation.
A
protein–protein
interaction
network
was
constructed,
cytoHubba
six
key
(BCL2,
MAPK14,
ABCB1,
PLK1,
ATM,
HMOX1).
Kaplan–Meier
immune
infiltration
further
showed
closely
prognosis
microenvironment
patients.
Single-cell
RNA
sequencing
expression
distribution
across
different
types
explored
roles
differentiation
process
malignant
cells
through
pseudotime
trajectory
analysis.
Molecular
docking
dynamics
simulation
results
indicated
Berberine-MAPK14
Matairesinol-PLK1
complexes
have
high
binding
affinity
stability.
Binding
free
energy
calculations
confirmed
stability
complexes.
Based
our
comprehensive
multi-level
analysis,
active
may
play
a
role
multi-target
synergistic
effects.
Successful
cancer
immunotherapy
requires
a
patient
to
mount
an
effective
immune
response
against
tumors;
however,
many
cancers
evade
the
body’s
system.
To
investigate
basis
for
treatment
failure,
we
examined
spontaneous
mouse
models
of
hepatocellular
carcinoma
(HCC)
with
either
inflamed
T
cell–rich
or
noninflamed
cell–deprived
tumor
microenvironment
(TME).
Our
studies
reveal
that
erythropoietin
(EPO)
secreted
by
cells
determines
immunotype.
Tumor-derived
EPO
autonomously
generates
TME
interacting
its
cognate
receptor
EPOR
on
tumor-associated
macrophages
(TAMs).
signaling
prompts
TAMs
become
immunoregulatory
through
NRF2-mediated
heme
depletion.
Removing
tumor-derived
leads
and
regression
independent
genotype,
owing
augmented
antitumor
cell
immunity.
Thus,
EPO/EPOR
axis
functions
as
immunosuppressive
switch
Antioxidants,
Год журнала:
2021,
Номер
10(5), С. 789 - 789
Опубликована: Май 17, 2021
Heme
oxygenase
1
(HO-1)
plays
a
key
role
in
cell
adaptation
to
stressors
through
the
antioxidant,
antiapoptotic,
and
anti-inflammatory
properties
of
its
metabolic
products.
For
these
reasons,
cancer
cells,
HO-1
can
favor
aggressiveness
resistance
therapies,
leading
poor
prognosis/outcome.
Genetic
polymorphisms
promoter
have
been
associated
with
an
increased
risk
progression
high
degree
therapy
failure.
Moreover,
evidence
from
biopsies
highlights
possible
correlation
between
expression,
pathological
features,
clinical
outcome.
Indeed,
levels
tumor
specimens
often
correlate
reduced
survival
rates.
Furthermore,
modulation
has
proposed
order
improve
efficacy
antitumor
therapies.
However,
contrasting
on
biology
reported.
This
review
focuses
as
promising
biomarker
progression;
understanding
data
might
guide
therapeutic
choice
outcome
patients
terms
prognosis
life
quality.
Journal of Extracellular Vesicles,
Год журнала:
2023,
Номер
12(5)
Опубликована: Май 1, 2023
Abstract
The
capture
of
tumour‐derived
extracellular
vesicles
(TEVs)
by
cells
in
the
tumour
microenvironment
(TME)
contributes
to
metastasis
and
notably
formation
pre‐metastatic
niche
(PMN).
However,
due
challenges
associated
with
modelling
release
small
EVs
vivo,
kinetics
PMN
response
endogenously
released
TEVs
have
not
been
examined.
Here,
we
studied
endogenous
mice
orthotopically
implanted
metastatic
human
melanoma
(MEL)
neuroblastoma
(NB)
releasing
GFP‐tagged
(GFTEVs)
their
host
demonstrate
active
contribution
metastasis.
Human
GFTEVs
captured
mouse
macrophages
vitro
resulted
transfer
GFP
exosomal
miR‐1246.
Mice
MEL
or
NB
showed
presence
blood
between
5
28
days
after
implantation.
Moreover,
kinetic
analysis
TEV
resident
relative
arrival
outgrowth
TEV‐producing
organs
demonstrated
that
lung
liver
precedes
homing
cells,
consistent
critical
roles
formation.
Importantly,
at
future
sites
was
miR‐1246
macrophages,
stellate
cells.
This
is
first
demonstration
organotropic
as
TEV‐capturing
only
absence
non‐metastatic
organs.
induced
dynamic
changes
inflammatory
gene
expression
which
evolved
a
pro‐tumorigenic
reaction
progressed
state.
Thus,
our
work
describes
novel
approach
tracking
vivo
provides
additional
insights
into
role
earliest
stages
progression.
Antioxidants,
Год журнала:
2023,
Номер
12(2), С. 220 - 220
Опубликована: Янв. 18, 2023
The
central
nervous
system
represents
a
complex
environment
in
which
glioblastoma
adapts
skillfully,
unleashing
series
of
mechanisms
suitable
for
its
efficient
development
and
diffusion.
In
particular,
changes
gene
expression
mutational
events
that
fall
within
the
domain
epigenetics
interact
complexly
with
metabolic
reprogramming
stress
responses
enacted
tumor
microenvironment,
turn
fuel
genomic
instability
by
providing
substrates
DNA
modifications.
aim
this
review
is
to
analyze
interaction
consolidates
several
conditions
confer
state
immunosuppression
immunoevasion,
making
capable
escaping
attack
elimination
immune
cells
therefore
invincible
against
current
therapies.
progressive
knowledge
cellular
underlie
resistance
represents,
fact,
only
weapon
unmask
weak
points
be
exploited
plan
successful
therapeutic
strategies.
Genes,
Год журнала:
2021,
Номер
12(9), С. 1364 - 1364
Опубликована: Авг. 30, 2021
The
production
of
around
2.5
million
red
blood
cells
(RBCs)
per
second
in
erythropoiesis
is
one
the
most
intense
activities
body.
It
continuously
consumes
large
amounts
iron,
approximately
80%
which
recycled
from
aged
erythrocytes.
Therefore,
similar
to
“making”,
“breaking”
also
very
rapid
and
represents
key
processes
mammalian
physiology.
Under
steady-state
conditions,
this
important
task
accomplished
by
specialized
macrophages,
mostly
liver
Kupffer
(KCs)
splenic
pulp
macrophages
(RPMs).
relies
a
extent
on
engulfment
via
so-called
erythrophagocytosis.
Surprisingly,
we
still
understand
little
about
mechanistic
details
removal
processing
these
macrophages.
We
have
only
started
uncover
signaling
pathways
that
imprint
their
identity,
control
functions
enable
plasticity.
Recent
findings
identify
other
myeloid
cell
types
capable
establish
reciprocal
cross-talk
between
intensity
erythrophagocytosis
cellular
activities.
Here,
aimed
review
multiple
emerging
facets
iron
recycling
illustrate
how
exciting
field
study
currently
expanding.
Journal for ImmunoTherapy of Cancer,
Год журнала:
2023,
Номер
11(3), С. e006433 - e006433
Опубликована: Март 1, 2023
Primary
and
secondary
resistance
is
a
major
hurdle
in
cancer
immunotherapy.
Therefore,
better
understanding
of
the
underlying
mechanisms
involved
immunotherapy
pivotal
importance
to
improve
therapy
outcome.Here,
two
mouse
models
with
against
therapeutic
vaccine-induced
tumor
regression
were
studied.
Exploration
microenvironment
by
high
dimensional
flow
cytometry
combination
vivo
settings
allowed
for
identification
immunological
factors
driving
resistance.Comparison
immune
infiltrate
during
early
late
revealed
change
from
tumor-rejecting
toward
tumor-promoting
macrophages.
In
concert,
rapid
exhaustion
tumor-infiltrating
T
cells
was
observed.
Perturbation
studies
identified
small
but
discernible
CD163hi
macrophage
population,
expression
several
markers
functional
anti-inflammatory
transcriptome
profile,
not
other
macrophages,
be
responsible.
In-depth
analyses
that
they
localize
at
invasive
margins
are
more
resistant
Csf1r
inhibition
when
compared
validated
activity
heme
oxygenase-1
as
an
mechanism
resistance.
The
transcriptomic
profile
macrophages
highly
similar
human
monocyte/macrophage
indicating
represent
target
efficacy.In
this
study,
population
tissue-resident
responsible
primary
T-cell-based
immunotherapies.
While
these
M2
Csf1r-targeted
therapies,
in-depth
characterization
allows
specific
targeting
subset
thereby
creating
new
opportunities
intervention
aim
overcome
Antioxidants,
Год журнала:
2023,
Номер
12(11), С. 1989 - 1989
Опубликована: Ноя. 10, 2023
Heme
oxygenase-1
(HO-1)
is
an
enzyme
located
at
the
endoplasmic
reticulum,
which
responsible
for
degradation
of
cellular
heme
into
ferrous
iron,
carbon
monoxide
and
biliverdin-IXa.
In
addition
to
this
main
function,
involved
in
many
other
homeostatic,
toxic
cancer-related
mechanisms.
review,
we
first
summarize
importance
HO-1
physiology
pathophysiology
with
a
focus
on
digestive
system.
We
then
detail
its
structure
followed
by
section
regulatory
mechanisms
that
control
expression
activity.
Moreover,
HO-2
as
important
further
HO
isoform
discussed,
highlighting
similarities
differences
regard
HO-1.
Subsequently,
describe
direct
indirect
cytoprotective
functions
breakdown
products
biliverdin-IXa,
but
also
highlight
possible
pro-inflammatory
effects.
Finally,
address
role
cancer
particular
colorectal
cancer.
Here,
relevant
pathways
are
presented,
through
impacts
tumor
induction
progression.
These
include
oxidative
stress
DNA
damage,
ferroptosis,
cell
cycle
progression
apoptosis
well
migration,
proliferation,
epithelial-mesenchymal
transition.
The EMBO Journal,
Год журнала:
2024,
Номер
43(8), С. 1445 - 1483
Опубликована: Март 18, 2024
Abstract
Regulatory
T
(TREG)
cells
develop
via
a
program
orchestrated
by
the
transcription
factor
forkhead
box
protein
P3
(FOXP3).
Maintenance
of
TREG
cell
lineage
relies
on
sustained
FOXP3
mechanism
involving
demethylation
cytosine-phosphate-guanine
(CpG)-rich
elements
at
conserved
non-coding
sequences
(CNS)
in
locus.
This
cytosine
is
catalyzed
ten–eleven
translocation
(TET)
family
dioxygenases,
and
it
involves
redox
reaction
that
uses
iron
(Fe)
as
an
essential
cofactor.
Here,
we
establish
human
mouse
express
Fe-regulatory
genes,
including
encoding
ferritin
heavy
chain
(FTH),
relatively
high
levels
compared
to
conventional
helper
cells.
We
show
FTH
expression
for
immune
homeostasis.
Mechanistically,
supports
TET-catalyzed
CpG-rich
CNS1
2
locus,
thereby
promoting
stability.
process,
which
stability
function,
limits
severity
autoimmune
neuroinflammation
infectious
diseases,
favors
tumor
progression.
These
findings
suggest
regulation
intracellular
stable
property
homeostasis
pathological
outcomes
immune-mediated
inflammation.