Toxics,
Journal Year:
2024,
Volume and Issue:
12(8), P. 620 - 620
Published: Aug. 22, 2024
The
utilization
of
contrast
media
(CM)
in
clinical
diagnostic
imaging
and
interventional
procedures
has
escalated,
leading
to
a
gradual
increase
the
incidence
contrast-induced
acute
kidney
injury
(CI-AKI).
Presently,
scarcity
effective
pharmacological
treatments
for
CI-AKI
poses
significant
challenges
management.
Firstly,
we
explore
pathogenesis
this
review.
Beyond
renal
medullary
ischemia
hypoxia,
oxidative
stress,
cellular
apoptosis,
inflammation,
emerging
mechanisms
such
as
ferroptosis,
release
neutrophil
extracellular
traps
(NETs),
nitrosative
which
offer
promising
avenues
management
CI-AKI,
are
identified.
Secondly,
comprehensive
strategy
early
prevention
is
introduced.
Investigating
risk
factors
associated
with
essential
timely
identification
high-risk
groups.
Additionally,
exploring
sensitive
biomarkers
crucial
diagnosis.
A
synergistic
approach
that
combines
these
biomarkers,
factors,
disease
prediction
models
enhances
both
accuracy
efficiency
processes.
Finally,
recent
non-pharmacological
interventions
Cl-AKI.
traditional
focus
on
antioxidant
N-acetylcysteine
(NAC),
look
at
active
compounds
from
Chinese
medicine,
including
tetramethylpyrazine
(TMP),
salvianolic
acid
B
(Sal
B),
well
preventive
medications
like
amide
(NACA),
alprostadil,
others,
all
showed
potential
benefits
animal
studies
prevention.
Furthermore,
innovative
strategies
calorie
restriction
(CR),
enhanced
external
counterpulsation
(EECP),
mesenchymal
stem
cell
therapy
highlighted
providing
fresh
insights
into
Cl-AKI
Molecular Biomedicine,
Journal Year:
2025,
Volume and Issue:
6(1)
Published: March 22, 2025
Abstract
Klotho,
initially
introduced
as
an
anti-aging
protein,
is
expressed
in
the
brain,
pancreas,
and
most
prominently
kidney.
The
two
forms
of
Klotho
(membrane-bound
soluble
form)
have
diverse
pharmacological
functions
such
anti-inflammatory,
anti-oxidative,
anti-fibrotic,
tumour-suppressive
etc.
membrane-bound
form
plays
a
pivotal
role
maintaining
kidney
homeostasis
by
regulating
fibroblast
growth
factor
23
(FGF
23)
signalling,
vitamin
D
metabolism
phosphate
balance.
deficiency
has
been
linked
with
significantly
reduced
protection
against
various
pathological
phenotypes,
including
diabetic
disease
(DKD),
which
major
cause
chronic
leading
to
end-stage
disease.
Owing
pleiotropic
actions
klotho,
it
shown
beneficial
effects
DKD
tackling
complex
pathophysiology
reducing
inflammation,
oxidative
stress,
well
fibrosis.
Moreover,
protective
effect
klotho
extends
beyond
other
conditions,
cardiovascular
diseases,
alzheimer's
disease,
cancer,
inflammatory
bowel
liver
Therefore,
this
review
summarizes
relationship
between
expression
diseases
special
emphasis
on
DKD,
distinct
mechanisms
potential
exogenous
supplementation
therapeutic
strategy.
Future
research
into
could
unravel
novel
treatment
avenues
for
diseases.
Cells,
Journal Year:
2024,
Volume and Issue:
13(17), P. 1413 - 1413
Published: Aug. 24, 2024
The
α-Klotho
protein
(hereafter
Klotho)
is
an
obligate
coreceptor
for
fibroblast
growth
factor
23
(FGF23).
It
produced
in
the
kidneys,
brain
and
other
sites.
Klotho
insufficiency
causes
hyperphosphatemia
anomalies.
Importantly,
it
associated
with
chronic
pathologies
(often
age-related)
that
have
inflammatory
component.
This
includes
atherosclerosis,
diabetes
Alzheimer's
disease.
Its
mode
of
action
these
diseases
not
well
understood,
but
inhibits
or
regulates
multiple
major
pathways.
has
a
membrane
form
soluble
(s-Klotho).
Cytosolic
postulated
characterized.
s-Klotho
endocrine
properties
are
incompletely
elucidated.
binds
to
FGF
receptor
1c
(FGFR1c)
widely
expressed
(including
endothelial
cells).
also
attaches
FGF23,
FGF23/Klotho
FGFRs.
Thus,
might
be
roaming
FGF23
coreceptor,
functions.
Notably,
(cell-bound
soluble)
counteracts
inflammation
appears
mitigate
related
aging
(inflammaging).
NF-κB
NLRP3
inflammasome.
inflammasome
requires
priming
by
produces
active
IL-1β,
pores
cell
death
(pyroptosis).
In
accord,
countered
injury
induced
toxins,
damage-associated
molecular
patterns
(DAMPs),
cytokines,
reactive
oxygen
species
(ROS).
blocks
TGF-β
Wnt
ligands,
which
lessens
fibrotic
Low
loss
muscle
mass
(sarcopenia),
as
occurs
diseases.
counters
inhibitory
effects
myostatin
on
muscle,
reduces
inflammation,
improves
repair
following
injury.
inhibition
factors
may
protective
diabetic
retinopathy
age-related
macular
degeneration
(AMD).
review
examines
functions
especially
potential
applications.
Kidney International,
Journal Year:
2023,
Volume and Issue:
104(5), P. 956 - 974
Published: Sept. 5, 2023
After
acute
kidney
injury
(AKI),
renal
tubular
epithelial
cells
(RTECs)
are
pathologically
characterized
by
intracellular
lipid
droplet
(LD)
accumulation,
which
involved
in
RTEC
and
fibrosis.
However,
its
pathogenesis
remains
incompletely
understood.
The
protein,
αKlotho,
primarily
expressed
RTECs,
is
well
known
as
an
anti-aging
hormone
wielding
versatile
functions,
membrane
form
predominantly
acts
a
co-receptor
for
fibroblast
growth
factor
23.
Here,
we
discovered
connection
between
αKlotho
LDs
RTECs.
Fluorescent
fatty
acid
(FA)
pulse-chase
assays
showed
that
deficiency
seen
homozygous
mutated
(kl/kl)
mice
or
with
ischemia-reperfusion
(IRI)-induced
AKI,
inhibited
FA
mobilization
from
impairing
adipose
triglyceride
lipase
(ATGL)-mediated
lipolysis
lipophagy.
This
resulted
LD
accumulation
underutilization.
IRI-induced
alterations
were
more
striking
deficiency.
Mechanistically,
promoted
E3
ligase
peroxin2
binding
to
ubiquitin-conjugating
enzyme
E2
D2,
resulting
ubiquitin-mediated
degradation
of
ATGL
common
molecular
basis
Overexpression
rescued
preventing
ubiquitination,
thereby
lessening
fibrosis
after
AKI.
suggests
indispensable
the
maintenance
homeostasis
Thus,
our
study
identified
critical
regulator
turnover
providing
viable
strategy
AKI-to-chronic
disease
transition.
Lipids in Health and Disease,
Journal Year:
2024,
Volume and Issue:
23(1)
Published: June 21, 2024
Abstract
Background
The
anti-aging
protein
Klotho
has
diverse
functions
in
antioxidative
stress
and
energy
metabolism
through
several
pathways.
While
it
been
reported
that
α-Klotho
is
downregulated
patients
with
insulin
resistance
(IR),
the
association
between
IR
complex
controversial.
triglyceride-glucose
(TyG)
index
provided
a
practical
method
for
assessing
IR.
With
this
mind,
our
study
aimed
to
investigate
relationship
TyG
soluble
levels
US
populations,
both
without
diabetes
mellitus.
Methods
This
cross-sectional
analyzed
data
from
middle-aged
older
participants
National
Health
Nutrition
Examination
Survey
(NHANES)
conducted
2007
2016.
were
divided
into
two
groups
based
on
their
mellitus
status:
those
diabetes.
To
evaluate
concentration
of
each
group,
series
survey-weighted
multivariable
linear
regression
models
employed.
Furthermore,
examine
these
variables,
multivariable-adjusted
restricted
cubic
spline
curves
subgroup
analysis
generated.
Results
involved
6,439
adults
aged
40
years
or
older,
mean
age
57.8
±
10.9
years.
Among
them,
1577
(24.5%)
had
A
indicated
presence
significantly
affected
level.
After
considering
all
covariables,
revealed
decreased
by
32.35
pg/ml
(95%
CI:
-50.07,
-14.64)
one
unit
increase
(
p
<
0.001).
decline
elevated
was
more
pronounced
female
population.
In
mellitus,
non-linear
observed.
There
no
significant
correlation
observed
when
below
9.7.
However,
there
an
klotho
106.44
above
9.7
28.13,
184.74)
=
0.008).
Conclusion
Our
findings
suggested
may
influence
α-Klotho.
seem
be
sex
differences
individuals
Further
studies
are
necessary
validate
findings.
BMC Nephrology,
Journal Year:
2024,
Volume and Issue:
25(1)
Published: June 7, 2024
Abstract
Objective
Contrast
media
(CM)
is
a
commonly
applied
drug
in
medical
examination
and
surgery.
However,
contrast-induced
acute
kidney
injury
(CIAKI)
poses
severe
threat
to
human
life
health.
Notably,
the
CUT-like
homeobox
1
(CUX1)
gene
shows
protective
effects
variety
of
cells.
Therefore,
objective
this
study
was
provide
new
target
for
treatment
CIAKI
through
exploring
role
possible
molecular
mechanism
CUX1
CIAKI.
Method
Blood
samples
were
collected
from
20
patients
with
healthy
volunteers.
Human
2
(HK-2)
cells
incubated
200
mg/mL
iohexol
6
h
establish
model
HK-2
Subsequently,
qRT-PCR
used
detect
relative
mRNA
expression
CUX1;
CCK-8
flow
cytometry
assess
proliferation
apoptosis
cells;
levels
IL(interleukin)-1β,
tumor
necrosis
factor
alpha
(TNF-α)
malondialdehyde
(MDA)
lactate
dehydrogenase
(LDH)
activity
cell
culture
supernatant
detect;
western
blot
observe
PI3K/AKT
signaling
pathway
related
proteins
[phosphorylated
phosphoinositide
3-kinase
(p-PI3K),
PI3K,
phosphorylated
Akt
(p-AKT),
AKT].
Results
significantly
downregulated
blood
(CM;
iohexol)
reduced
cells,
promoted
apoptosis,
stimulated
inflammation
oxidative
stress
that
caused
damage.
overexpression
alleviated
damage
by
improving
level
induced
CM,
inhibiting
reducing
LDH
IL-1β,
TNF-α
MDA
CM
inhibited
activity.
Nevertheless,
up-regulating
could
activate
CM.
Conclusion
promotes
proliferation,
inhibits
reduces
CM-induced
alleviate
The
may
be
correlated
activation
pathway.
Shock,
Journal Year:
2024,
Volume and Issue:
62(3), P. 447 - 456
Published: June 21, 2024
ABSTRACT
Diabetes
and
myocardial
ischemia
reperfusion
(MIR)
injury
are
characterized
by
oxidative
stress,
inflammation,
autophagy
disorders,
cardiac
contractile
dysfunction.
Klotho
SIRT1
regulate
the
level
of
stress
to
participate
in
regulation
many
physiological
functions
such
as
cell
survival,
aging,
apoptosis,
autophagy,
mitochondrial
biogenesis,
inflammation.
We
hypothesized
that
activation
Klotho/SIRT1
signaling
pathway
could
attenuate
MIR
diabetic
rats.
Type
1
diabetes
model
were
established
examine
this
hypothesis
vivo
.
Primary
rat
cardiomyocytes
H9c2
cells
exposed
high
glucose
conditions
hypoxia/reoxygenation
(H/R)
insult
vitro
Hemodynamic
parameters
heart
function,
infarct
size,
markers
or
viability,
mRNA
protein
expression
measured.
There
was
lower
hearts
than
nondiabetic
rats,
well
significantly
increased
levels
decreased
levels.
Recombinant
(rKlotho)
agonist
SRT1720
activating
reduce
restore
These
findings
suggest
plays
an
important
role
rKlotho
have
therapeutic
potential
for
alleviating
IR
The
α-Klotho
protein
(hereafter
Klotho)
is
an
obligate
coreceptor
for
fibroblast
growth
factor
23
(FGF23).
It
produced
in
the
kidneys,
brain
and
other
sites.
Klotho
insufficiency
causes
hyperphosphatemia
anomalies.
Importantly,
it
associated
with
chronic
pathologies
(often
age-related)
that
have
inflammatory
component.
This
includes
atherosclerosis,
diabetes
Alzheimer’s
disease.
Its
mode
of
action
these
diseases
not
well
understood,
but
inhibits
or
regulates
multiple
major
pathways.
has
a
membrane
form,
soluble
form
(s-Klotho).
Cytosolic
postulated
characterized.
s-Klotho
endocrine
properties
are
incompletely
elucidated.
binds
to
FGF
receptor
1c
(FGFR1c)
widely
expressed
(including
endothelial
cells).
also
attaches
FGF23,
FGF23/Klotho
FGFRs.
Thus,
might
be
roaming
FGF23
coreceptor,
functions.
Notably,
(cell-bound
soluble)
counteracts
inflammation,
appears
mitigate
related
aging
(inflammaging).
NF-κB
NLRP3
inflammasome.
inflammasome
requires
priming
by
NF-κB,
produces
active
IL-1β,
pores
cell
death
(pyroptosis).
In
accord,
countered
inflammation
injury
induced
toxins,
damage-associated
molecular
patterns
(DAMPs),
cytokines,
reactive
oxygen
species
(ROS).
blocks
TGF-β
Wnt
ligands,
which
lessens
fibrotic
Low
loss
muscle
mass
(sarcopenia),
as
occurs
diseases.
counters
inhibitory
effects
myostatin
on
muscle,
reduces
improves
repair
following
injury.
Inhibition
factors
may
protective
diabetic
retinopathy
age-related
macular
degeneration
(AMD).
review
examines
functions
especially
potential
applications.