Pharmaceutics,
Journal Year:
2020,
Volume and Issue:
12(5), P. 434 - 434
Published: May 8, 2020
Patients
with
acute
kidney
injury
(AKI)
who
survive
the
stage
are
at
notable
risk
for
chronic
disease
(CKD)
progression.
There
is
no
single
therapy
that
can
effectively
prevent
AKI
to
CKD
transition.
Autophagy
a
cytoplasmic
component
degradation
pathway
and
has
complex
functions
in
several
diseases,
such
as
renal
fibrosis.
Previous
research
shown
lactoferrin
important
antioxidant
defense
other
systems,
protecting
kidneys
against
various
injuries.
The
present
study
investigated
effect
of
We
identified
62
consensus
genes
two-fold
changes
clinical
tissues
from
patients.
Among
overlay
genes,
mRNA
levels
LTF
were
significantly
upregulated
Lactoferrin
induced
autophagy
via
activation
AMPK
inhibition
Akt/mTOR
human
proximal
tubular
cells.
suppressed
oxidative
stress-induced
cell
death
apoptosis
by
augmenting
autophagy.
an
antifibrotic
role
In
mouse
model
folic
acid-induced
transition,
treatment
recovered
function
further
fibrosis
through
induction
These
findings
identify
potential
therapeutic
target
prevention
International Journal of Molecular Sciences,
Journal Year:
2020,
Volume and Issue:
21(8), P. 2987 - 2987
Published: April 23, 2020
Recent
data
have
indicated
the
emerging
role
of
glomerular
autophagy
in
diabetic
kidney
disease.
We
aimed
to
assess
effect
SGLT2
inhibitor
empagliflozin,
DPP4
linagliptin,
and
their
combination,
on
a
model
type
2
diabetes.
Eight-week-old
male
db/db
mice
were
randomly
assigned
treatment
with
empagliflozin–linagliptin
or
vehicle
for
8
weeks.
Age-matched
non-diabetic
db/+
acted
as
controls.
To
estimate
autophagy,
immunohistochemistry
beclin-1
LAMP-1
was
performed.
Podocyte
assessed
by
counting
volume
density
(Vv)
autophagosomes,
lysosomes
autolysosomes
transmission
electron
microscopy.
LC3B
LAMP-1,
markers,
caspase-3
Bcl-2,
apoptotic
evaluated
renal
cortex
western
blot.
Vehicle-treated
had
weak
staining
reduced
Vv
podocytes.
Empagliflozin
both
monotherapy
enhanced
areas
increased
autophagosomes
Renal
Bcl-2
restored
actively
treated
animals.
expression
empagliflozin
group;
decreased
group
only.
Mesangial
expansion,
podocyte
foot
process
effacement
urinary
albumin
excretion
mitigated
agents.
The
provide
further
explanation
mechanism
renoprotective
inhibitors
Diabetes Obesity and Metabolism,
Journal Year:
2021,
Volume and Issue:
24(3), P. 365 - 376
Published: Nov. 15, 2021
Based
on
global
estimates,
almost
10%
of
adults
have
diabetes,
whom
40%
are
estimated
to
also
chronic
kidney
disease
(CKD).
Almost
2
decades
ago,
treatments
targeting
the
renin-angiotensin
system
(RAS)
were
shown
slow
progression
disease.
More
recently,
studies
reported
additive
benefits
antihyperglycaemic
sodium-glucose
co-transporter-2
inhibitors
in
combination
with
RAS
both
CKD
and
cardiovascular
outcomes.
However,
these
recent
data
showed
that
patients
continue
progress
failure
or
die
from
kidney-
cardiovascular-related
causes.
Therefore,
new
agents
needed
address
this
continuing
risk.
Overactivation
mineralocorticoid
(MR)
receptor
contributes
inflammation
fibrosis,
suggesting
it
is
an
appropriate
treatment
target
diabetes
CKD.
Novel,
selective
non-steroidal
MR
antagonists
being
studied
patients,
results
two
large
recently
completed
clinical
trials
one
such
treatment,
finerenone,
significantly
reduces
events
compared
standard
care.
This
review
summarizes
pathogenic
mechanisms
type
examines
potential
benefit
novel
disease-modifying
inflammatory
fibrotic
factors
patients.
International Journal of Molecular Sciences,
Journal Year:
2021,
Volume and Issue:
22(15), P. 7783 - 7783
Published: July 21, 2021
A
growing
body
of
evidence
points
to
the
role
glucose
variability
(GV)
in
development
microvascular
and
macrovascular
complications
diabetes.
In
this
review,
we
summarize
data
on
GV-induced
biochemical,
cellular
molecular
events
involved
pathogenesis
diabetic
complications.
Current
indicate
that
deteriorating
effect
GV
target
organs
can
be
realized
through
oxidative
stress,
glycation,
chronic
low-grade
inflammation,
endothelial
dysfunction,
platelet
activation,
impaired
angiogenesis
renal
fibrosis.
The
effects
dysfunction
hypercoagulability
could
aggravated
by
hypoglycemia,
associated
with
high
GV.
Oscillating
hyperglycemia
contributes
beta
cell
which
leads
a
further
increase
completes
vicious
circle.
cells,
cytotoxic
includes
mitochondrial
endoplasmic
reticulum
stress
disturbances
autophagic
flux,
are
accompanied
reduced
viability,
activation
apoptosis
abnormalities
proliferation.
These
up-
down-regulation
large
number
genes
activity
signaling
pathways
such
as
PI3K/Akt,
NF-κB,
MAPK
(ERK),
JNK
TGF-β/Smad.
Epigenetic
modifications
mediate
postponed
fluctuations.
multiple
deteriorative
provide
support
for
considering
it
therapeutic
Journal of the American Society of Nephrology,
Journal Year:
2021,
Volume and Issue:
32(7), P. 1559 - 1567
Published: May 28, 2021
The
effectiveness
of
cisplatin,
a
mainstay
in
the
treatment
many
solid
organ
cancers,
is
hindered
by
dose-limiting
nephrotoxicity.
Cisplatin
causes
AKI
30%
patients.
Patients
who
do
not
develop
clinical
standards
during
are
still
at
risk
for
long-term
decline
kidney
function
and
development
CKD.
connection
between
CKD
has
become
increasingly
studied,
with
renal
fibrosis
hallmark
development.
To
prevent
both
short-
effects
researchers
must
use
models
that
reflect
types
pathology.
Although
lot
known
about
cisplatin-induced
AKI,
very
little
mechanisms
which
repeated
low
levels
cisplatin
lead
to
In
this
review,
strategies
used
various
rodent
injury,
its
progression
fibrosis,
or
both,
examined
gain
mechanistic
insights
identify
potential
therapeutic
targets
pathologies.
Reviewing
results
from
these
highlights
diverse
highly
complex
role
cell
death,
senescence,
endoplasmic
reticulum
stress,
autophagy,
immune
activation
acute
chronic
injuries.
several
injury
needed
agents
will
all
aspects
injury.
Medical Science Monitor,
Journal Year:
2022,
Volume and Issue:
28
Published: Aug. 10, 2022
Diabetic
nephropathy
is
a
common
complication
of
type
I
and
II
diabetes,
in
which
renal
glomeruli
are
destroyed,
resulting
damage,
proteinuria,
hypertension.
Apoptosis,
autophagy,
necroptosis
3
forms
programmed
cell
death
that
have
been
implicated
the
pathogenesis
diabetic
nephropathy.
Apoptosis
podocytes
leads
to
glomerular
injury
podocyte
depletion,
associated
with
proteinuria
structural
damage
Additionally,
epithelial
cells
proximal
convoluted
tubules
also
undergo
apoptosis
nephropathy,
leading
tubular
atrophy,
causes
depletion
subsequent
formation
atubular
association
loss
function.
On
other
hand,
insufficiency
autophagy
has
correlated
For
instance,
decreased
autophagic
activity
shown
kidney,
causing
variations
function
disruption
filtration
barrier.
Furthermore,
attenuated
demonstrated
buildup
impaired
molecules
organelles,
normally
broken
down
by
proteinuria.
Moreover,
might
key
role
decline
Thus,
this
article
aims
review
mechanisms
effects
including
roles
apoptosis,
necroptosis.
The American Journal of Chinese Medicine,
Journal Year:
2022,
Volume and Issue:
50(07), P. 1739 - 1779
Published: Jan. 1, 2022
Diabetic
nephropathy
(DN)
is
a
common
microvascular
complication
of
diabetes
mellitus
(DM),
which
can
lead
to
renal
failure
in
diabetic
patients.
At
present,
the
first-line
drugs
for
DN
are
mainly
renin–angiotensin
system
(RAS)
inhibitors
or
angiotensin
receptor
blockers,
and
latest
approved
aldosterone
antagonist
finerenone,
delay
progression
end-stage
disease
(ESRD),
but
therapeutic
effect
still
not
ideal.
With
history
thousands
years,
traditional
Chinese
medicine
(TCM)
has
rich
experience
treatment
DN.
Based
on
theory
TCM,
clinical
focuses
generating
fluid
nourishing
blood,
Qi
Yin,
detoxifying
detumescent.
In
recently
effects
mechanisms
TCM
prescription,
herbal
medicine,
its
active
components
have
received
extensive
attention
new
drug
development.
This
paper
reviews
research
progress
mechanism
Frontiers in Endocrinology,
Journal Year:
2023,
Volume and Issue:
14
Published: March 20, 2023
Diabetic
nephropathy
(DN),
the
leading
cause
of
end-stage
renal
disease,
is
most
significant
microvascular
complication
diabetes
and
poses
a
severe
public
health
concern
due
to
lack
effective
clinical
treatments.
Autophagy
lysosomal
process
that
degrades
damaged
proteins
organelles
preserve
cellular
homeostasis.
Emerging
studies
have
shown
disorder
in
autophagy
results
accumulation
diabetic
cells
promotes
development
DN.
regulated
by
nutrient-sensing
pathways
including
AMPK,
mTOR,
Sirt1,
several
intracellular
stress
signaling
such
as
oxidative
endoplasmic
reticulum
stress.
An
abnormal
nutritional
status
excess
stresses
caused
diabetes-related
metabolic
disorders
disturb
autophagic
flux,
dysfunction
Here,
we
summarized
role
DN
focusing
on
modulate
therapeutic
interferences
Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
15
Published: March 1, 2024
Cardiac
fibrosis
is
a
serious
health
problem
because
it
common
pathological
change
in
almost
all
forms
of
cardiovascular
diseases.
characterized
by
the
transdifferentiation
cardiac
fibroblasts
(CFs)
into
myofibroblasts
and
excessive
deposition
extracellular
matrix
(ECM)
components
produced
activated
myofibroblasts,
which
leads
to
fibrotic
scar
formation
subsequent
dysfunction.
However,
there
are
currently
few
effective
therapeutic
strategies
protecting
against
fibrogenesis.
This
lack
largely
molecular
mechanisms
remain
unclear
despite
extensive
research.
The
Janus
kinase/signal
transducer
activator
transcription
(JAK/STAT)
signaling
cascade
an
extensively
present
intracellular
signal
transduction
pathway
can
regulate
wide
range
biological
processes,
including
cell
proliferation,
migration,
differentiation,
apoptosis,
immune
response.
Various
upstream
mediators
such
as
cytokines,
growth
factors
hormones
initiate
transmission
via
this
play
corresponding
regulatory
roles.
STAT3
crucial
player
JAK/STAT
its
activation
related
inflammation,
malignant
tumors
autoimmune
illnesses.
Recently,
JAK/STAT3
has
been
spotlight
for
role
occurrence
development
promote
proliferation
CFs
production
ECM
proteins,
thus
leading
fibrosis.
In
manuscript,
we
discuss
structure,
transactivation
regulation
review
recent
progress
on
Moreover,
summarize
current
challenges
opportunities
targeting
treatment
summary,
information
presented
article
critical
comprehending
fibrosis,
will
also
contribute
future
research
aimed
at
anti-fibrotic
signaling.