ACS Nano,
Год журнала:
2023,
Номер
17(23), С. 23608 - 23625
Опубликована: Ноя. 23, 2023
Liver
fibrosis
is
a
major
contributor
to
the
morbidity
and
mortality
associated
with
liver
diseases,
yet
effective
treatment
options
remain
limited.
Hepatic
stellate
cells
(HSCs)
are
promising
target
for
hepatic
fibrogenesis
due
their
pivotal
role
in
disease
progression.
Our
previous
research
has
demonstrated
potential
of
Dihydrotanshinone
I
(DHI),
lipophilic
component
derived
from
natural
herb
Salvia
miltiorrhiza
Bunge,
treating
by
inhibiting
YAP/TEAD2
interaction
HSCs.
However,
clinical
application
DHI
faces
challenges
its
poor
aqueous
solubility
lack
specificity
Additionally,
recent
studies
have
implicated
impact
microbiota,
distinct
gut
on
pathogenesis
diseases.
In
this
study,
we
developed
an
HSC-
microbiome-specific
delivery
system
conjugating
prebiotic-like
cyclodextrin
(CD)
vitamin
A,
utilizing
PEG2000
as
linker
(VAP2000@CD).
results
demonstrate
that
VAP2000@CD
markedly
enhances
cellular
uptake
human
HSC
line
LX-2
deposition
fibrotic
vivo.
Subsequently,
intervention
DHI-VAP2000@CD
shown
notable
reduction
bile
duct-like
structure
proliferation,
collagen
accumulation,
expression
fibrogenesis-associated
genes
rats
subjected
duct
ligation.
These
effects
may
be
attributed
regulation
interaction.
Importantly,
also
restored
microbial
homeostasis
liver,
promoting
amelioration
inflammation.
Overall,
our
findings
indicate
represents
therapeutic
approach
specifically
targeting
HSCs
restoring
balance.
Frontiers in Immunology,
Год журнала:
2021,
Номер
12
Опубликована: Дек. 14, 2021
Macrophages
are
important
immune
cells
in
innate
immunity,
and
have
remarkable
heterogeneity
polarization.
Under
pathological
conditions,
addition
to
the
resident
macrophages,
other
macrophages
also
recruited
diseased
tissues,
polarize
various
phenotypes
(mainly
M1
M2)
under
stimulation
of
factors
microenvironment,
thus
playing
different
roles
functions.
Liver
diseases
hepatic
changes
caused
by
a
variety
pathogenic
(viruses,
alcohol,
drugs,
etc.),
including
acute
liver
injury,
viral
hepatitis,
alcoholic
disease,
metabolic-associated
fatty
fibrosis,
hepatocellular
carcinoma.
Recent
studies
shown
that
macrophage
polarization
plays
an
role
initiation
development
diseases.
However,
because
both
pathogenesis
complex,
mechanism
need
be
further
clarified.
Therefore,
origin
mechanisms
reviewed
first
this
paper.
It
is
found
involves
several
molecular
mechanisms,
mainly
TLR4/NF-κB,
JAK/STATs,
TGF-β/Smads,
PPARγ,
Notch,
miRNA
signaling
pathways.
In
addition,
paper
expounds
diseases,
which
aims
provide
references
for
research
contributing
therapeutic
strategy
ameliorating
modulating
Redox Biology,
Год журнала:
2024,
Номер
69, С. 103029 - 103029
Опубликована: Янв. 4, 2024
Hepatocyte
ferroptosis
promotes
the
pathogenesis
and
progression
of
liver
fibrosis.
Salvianolic
acid
B
(Sal
B)
exerts
antifibrotic
effects.
However,
pharmacological
mechanism
target
has
not
yet
been
fully
elucidated.
In
this
study,
fibrosis
was
induced
by
CCl4
in
wild-type
mice
hepatocyte-specific
extracellular
matrix
protein
1
(Ecm1)-deficient
mice,
which
were
separately
treated
with
Sal
B,
ferrostatin-1,
sorafenib
or
cilengitide.
Erastin-
CCl4-induced
hepatocyte
models
without
Ecm1
gene
knockdown
evaluated
vitro.
Subsequently,
interaction
between
xCT
binding
kinetics
determined.
We
found
that
significantly
attenuated
mice.
deletion
hepatocytes
abolished
effect
B.
Mechanistically,
protected
against
upregulating
Ecm1.
Further
research
revealed
as
a
direct
for
treating
Interestingly,
interacted
to
regulate
ferroptosis.
vitro
treatment,
abrogated
after
LO2
cells.
Therefore,
alleviates
targeting
up-regulation
inhibiting
The
regulates
Stem Cell Research & Therapy,
Год журнала:
2022,
Номер
13(1)
Опубликована: Май 3, 2022
Abstract
Mesenchymal
stem
cell
(MSC)
transplantation,
as
an
alternative
strategy
to
orthotopic
liver
has
been
evaluated
for
treating
end-stage
disease.
Although
the
therapeutic
mechanism
of
MSC
transplantation
remains
unclear,
accumulating
evidence
demonstrated
that
MSCs
can
regenerate
tissues
and
self-renew
repair
through
differentiation
into
hepatocyte-like
cells,
immune
regulation,
anti-fibrotic
mechanisms.
Multiple
clinical
trials
have
confirmed
restores
function
alleviates
damage.
A
sufficient
number
must
be
home
target
after
administration
successful
application.
However,
inefficient
homing
systemic
is
a
major
limitation
in
therapy.
Here,
we
review
mechanisms
application
status
treatment
disease
comprehensively
summarize
molecular
homing,
various
strategies
promoting
improve
Aging and Disease,
Год журнала:
2023,
Номер
14(3), С. 670 - 670
Опубликована: Янв. 1, 2023
The
biomechanical
properties
of
extracellular
matrices
(ECM)
and
their
consequences
for
cellular
homeostasis
have
recently
emerged
as
a
driver
aging.
Here
we
review
the
age-dependent
deterioration
ECM
in
context
our
current
understanding
aging
processes.
We
discuss
reciprocal
interactions
longevity
interventions
with
remodeling.
And
relevance
dynamics
captured
by
matrisome
matreotypes
associated
health,
disease,
longevity.
Furthermore,
highlight
that
many
established
compounds
promote
homeostasis.
A
large
body
evidence
to
qualify
hallmark
is
emerging,
data
invertebrates
promising.
However,
direct
experimental
proof
activating
sufficient
slow
mammals
lacking.
conclude
further
research
required
anticipate
conceptual
framework
biomechanics
will
provide
new
strategies
health
during
Intracellular
lipid
accumulation
is
commonly
seen
in
fibrotic
livers,
but
its
exact
role
liver
fibrosis
remains
elusive.
Here,
we
established
a
multimodal
nonlinear
optical
microscopy
to
quantitatively
map
distribution
of
biomolecules
livers.
Our
data
revealed
that
unsaturated
triglycerides
were
predominantly
accumulated
central
vein
area
during
not
portal
area.
Moreover,
the
homeostasis
was
remarkably
dysregulated
late-stage
compared
early-stage
fibrosis,
including
increased
with
decreased
unsaturation
degree
and
membrane
fluidity.
Such
alterations
likely
due
up-regulated
lipogenesis,
desaturation,
peroxidation,
which
consequently
led
endoplasmic
reticulum
stress
cell
death.
Inspiringly,
injured
hepatocyte
could
be
rescued
by
remodeling
via
either
supply
fatty
acids
or
enhancement
Collectively,
our
study
improves
current
understanding
open
opportunities
for
treatment.
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Март 20, 2023
Liver
fibrosis
is
a
global
health
problem
caused
by
chronic
liver
injury
resulting
from
various
factors.
Hepatic
stellate
cells
(HSCs)
have
been
found
to
play
major
role
in
fibrosis,
and
pathological
stimuli
lead
their
transdifferentiation
into
myofibroblasts.
Complex
multidirectional
interactions
between
HSCs,
immune
cells,
cytokines
are
also
critical
for
the
progression
of
fibrosis.
Despite
advances
treatments
they
do
not
meet
current
medical
needs.
Exosomes
extracellular
vesicles
30-150
nm
diameter
capable
intercellular
transport
molecules
such
as
lipids,
proteins
nucleic
acids.
As
an
essential
mediator
communication,
exosomes
involved
physiological
processes
many
diseases.
In
pathogenesis
mainly
regulating
activation
HSCs
interaction
cells.
Serum-derived
promising
biomarkers
therapeutic
potential
derived
mesenchymal
stem
other
exhibit
anti-liver
effects.
Moreover,
may
serve
targets
hold
promise
becoming
drug
carriers
treatment.
