Proceedings of the National Academy of Sciences,
Год журнала:
2018,
Номер
115(41), С. 10511 - 10516
Опубликована: Сен. 24, 2018
Effective
delivery
of
drug
carriers
selectively
to
the
kidney
is
challenging
because
their
uptake
by
reticuloendothelial
system
in
liver
and
spleen,
which
limits
effective
treatment
diseases
results
side
effects.
To
address
this
issue,
we
synthesized
l-serine
(Ser)-modified
polyamidoamine
dendrimer
(PAMAM)
as
a
potent
renal
targeting
carrier.
Approximately
82%
dose
was
accumulated
at
3
h
after
i.v.
injection
111In-labeled
Ser-PAMAM
mice,
while
unmodified
PAMAM,
l-threonine
modified
l-tyrosine
PAMAM
resulted
accumulations
28%,
35%,
31%,
respectively.
Single-photon
emission
computed
tomography/computed
tomography
(SPECT/CT)
images
also
indicated
that
specifically
kidneys.
An
intrakidney
distribution
study
showed
fluorescein
isothiocyanate-labeled
predominantly
proximal
tubules.
Results
cellular
LLC-PK1
cells
presence
inhibitors
[genistein,
5-(N-ethyl-N-isopropyl)amiloride,
lysozyme]
revealed
caveolae-mediated
endocytosis,
micropinocytosis,
megalin
were
associated
with
accumulation
Ser-PAMAM.
The
efficient
angiotensin-converting
enzyme
(ACE)
inhibition
effect
captopril
(CAP),
an
ACE
inhibitor,
observed
Ser-PAMAM-CAP
conjugate.
These
findings
indicate
promising
carrier
for
diseases.
Thus,
demonstrate
via
Ser
modification.
Journal of Molecular Medicine,
Год журнала:
2024,
Номер
102(4), С. 537 - 570
Опубликована: Фев. 29, 2024
Abstract
Diabetes
mellitus
(DM)
often
causes
chronic
kidney
damage
despite
best
medical
practices.
Diabetic
disease
(DKD)
arises
from
a
complex
interaction
of
factors
within
the
and
whole
body.
Targeting
specific
disease-causing
agents
using
drugs
has
not
been
effective
in
treating
DKD.
However,
stem
cell
therapies
offer
promising
alternative
by
addressing
multiple
pathways
promoting
regeneration.
Mesenchymal
cells
(MSCs)
great
promise
due
to
their
superior
accessibility
ratio
adult
tissues
remarkable
modes
action,
such
as
production
paracrine
anti-inflammatory
cytoprotective
substances.
This
review
critically
evaluates
development
MSC
treatment
for
DKD
it
moves
closer
clinical
application.
Results
animal
models
suggest
that
systemic
infusion
may
positively
impact
progression.
few
registered
completed
trials
exist,
whether
treatments
are
humans
is
still
being
determined.
Significant
knowledge
gaps
research
opportunities
including
establishing
ideal
source,
dose,
timing
delivery,
better
understanding
vivo
mechanisms,
developing
quantitative
indicators
obtain
more
significant
therapeutic
response.
paper
reviews
recent
literature
on
MSCs
preclinical
Potent
biomarkers
related
also
highlighted,
which
help
understand
MSCs’
action
this
Key
messages
have
effects
diabetic
disease.
alleviate
having
possess
Cell Biology International,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 27, 2025
ABSTRACT
Acute
kidney
injury
(AKI)
in
diabetic
conditions
often
advances
to
chronic
disease
(CKD),
exacerbated
by
ischemia–reperfusion
(IRI)
through
pathomechanisms
such
as
endoplasmic
reticulum
(ER)
stress
and
inflammation.
Currently,
available
treatment
options
for
AKI
are
not
uniformly
effective,
highlighting
the
need
novel
interventions.
This
study
aimed
examine
renoprotective
effects
of
hinokitiol,
a
natural
tropolone
compound,
against
with
its
capability
decrease
ER
inflammation,
along
apoptosis.
involved
NRK‐52E
cells
grown
in‐vitro
under
high‐glucose
subjected
10
mM
sodium
azide
elicit
hypoxia/reperfusion
(HRI).
The
expression
key
markers
like
binding
immunoglobulin
protein
(BiP),
R/PKR‐like
kinase
(PERK),
eukaryotic
initiation
factor‐2
(eIF2α)
well
inflammatory
proteins
was
markedly
diminished
hinokitiol
pretreatment
(50
μM).
Hinokitiol
further
reduced
apoptosis
cells.
Similarly,
in‐vivo
study,
male
Wistar
rats
STZ‐induced
Type
1
diabetes
(55
mg/kg,
i.p
.)
were
treated
50
100
mg/kg/day
.
5
days,
followed
induction
via
bilateral
IRI.
significantly
elevated
plasma
blood
urea
nitrogen
(BUN),
creatinine,
urinary
molecule‐1
(KIM‐1)
levels
tubular
damage
rats.
also
respective
expressions
rats,
demonstrated
immunohistochemical
analysis
immunoblotting.
These
findings
suggest
that
alleviates
modulating
PERK/CHOP/NF‐κB
axis,
likeliness
viable
therapeutic
technique
alleviating
AKI.
Theranostics,
Год журнала:
2019,
Номер
9(21), С. 6191 - 6208
Опубликована: Янв. 1, 2019
The
optimization
of
nanoparticle
size
for
passing
through
glomerular
filtration
membrane,
inefficient
renal
cellular
uptake
and
rapid
urinary
excretion
nanoparticles
are
the
major
obstacles
disease
treatment
via
a
delivery
system.
Herein,
we
propose
concept
two-step
nanoparticular
cascade
control
enhancement
to
overcome
obstacles.
Methods:
We
prepared
kidney-targeted
rhein
(RH)-loaded
liponanoparticles
(KLPPR)
with
yolk-shell
structure
composed
by
polycaprolactone-polyethyleneimine
(PCL-PEI)-based
cores
kidney
targeting
peptide
(KTP)-modified
lipid
layers.
KLPPR
within
range
30
~
80
nm
allowed
distribute
into
membrane
KTP
(sequence:
CSAVPLC)
decoration
promoted
endocytosis
non-lysosomal
pathway.
Results:
had
an
average
59.5±6.2
exhibited
high
RH
loading,
sustained
release,
good
stability
biocompatibility,
in
HK-2
cells.
In
addition,
intravenous
administration
resulted
excellent
distribution
low
mice
streptozocin-induced
diabetic
nephropathy
(DN),
lowered
parameters
urea
nitrogen,
serum
creatinine
index,
as
well
facilitated
recovery
physiological
function
improving
levels
clearance
rate
suppressing
secretion
accumulation
fibronectin
TGF-β1.
Conclusion:
Definitely,
were
able
target
diseased
improve
therapeutic
effect
on
DN
exploiting
uptake.
This
study
offers
promising
strategy
diseases
using
liponanoparticle
Diabetes,
Год журнала:
2020,
Номер
69(11), С. 2229 - 2237
Опубликована: Окт. 14, 2020
The
landscape
of
kidney
disease
in
diabetes
has
shifted.
classical
dogma
“diabetic
nephropathy”
progressing
through
stages
albuminuria,
leading
to
decline
glomerular
filtration
rate
and
end-stage
(ESKD),
been
replaced
by
a
more
nuanced
understanding
the
complex
heterogeneous
nature
diabetes.
Paralleling
this
evolution,
standardized
definitions
have
resulted
growing
appreciation
that
acute
injury
(AKI)
is
increasing
its
incidence
rapidly
people
with
are
much
likely
develop
AKI
than
without
Here,
I
propose
should
be
considered
complication
alongside
other
complications
similarly
do
not
fit
neatly
into
historical
microvascular/macrovascular
paradigm.
In
article,
we
take
look
at
evidence
indicating
major
risk
factor
for
review
causes
increased
risk.
We
consider
long-term
implications
potential
contribution
future
development
chronic
disease,
ESKD,
mortality.
Finally,
toward
strategies
better
identify
new
approaches
improve
outcomes.
Recognizing
as
bona
fide
open
up
avenues
investigation
may
ultimately
outlook
living
disease.
Proceedings of the National Academy of Sciences,
Год журнала:
2018,
Номер
115(41), С. 10511 - 10516
Опубликована: Сен. 24, 2018
Effective
delivery
of
drug
carriers
selectively
to
the
kidney
is
challenging
because
their
uptake
by
reticuloendothelial
system
in
liver
and
spleen,
which
limits
effective
treatment
diseases
results
side
effects.
To
address
this
issue,
we
synthesized
l-serine
(Ser)-modified
polyamidoamine
dendrimer
(PAMAM)
as
a
potent
renal
targeting
carrier.
Approximately
82%
dose
was
accumulated
at
3
h
after
i.v.
injection
111In-labeled
Ser-PAMAM
mice,
while
unmodified
PAMAM,
l-threonine
modified
l-tyrosine
PAMAM
resulted
accumulations
28%,
35%,
31%,
respectively.
Single-photon
emission
computed
tomography/computed
tomography
(SPECT/CT)
images
also
indicated
that
specifically
kidneys.
An
intrakidney
distribution
study
showed
fluorescein
isothiocyanate-labeled
predominantly
proximal
tubules.
Results
cellular
LLC-PK1
cells
presence
inhibitors
[genistein,
5-(N-ethyl-N-isopropyl)amiloride,
lysozyme]
revealed
caveolae-mediated
endocytosis,
micropinocytosis,
megalin
were
associated
with
accumulation
Ser-PAMAM.
The
efficient
angiotensin-converting
enzyme
(ACE)
inhibition
effect
captopril
(CAP),
an
ACE
inhibitor,
observed
Ser-PAMAM-CAP
conjugate.
These
findings
indicate
promising
carrier
for
diseases.
Thus,
demonstrate
via
Ser
modification.
