EMBO Molecular Medicine,
Год журнала:
2021,
Номер
13(5)
Опубликована: Май 3, 2021
miRNAs
have
emerged
as
critical
regulators
of
nearly
all
biologic
processes
and
important
therapeutic
targets
for
numerous
diseases.
However,
despite
the
tremendous
progress
that
has
been
made
in
this
field,
many
misconceptions
remain
among
much
broader
scientific
community
about
manner
which
function.
In
review,
we
focus
on
miR-33,
one
most
extensively
studied
miRNAs,
an
example,
to
highlight
advances
miRNA
field
hurdles
must
be
cleared
promote
development
miRNA-based
therapies.
We
discuss
how
generation
novel
animal
models
newly
developed
experimental
techniques
helped
elucidate
specialized
roles
miR-33
within
different
tissues
begin
define
specific
mechanisms
by
contributes
cardiometabolic
diseases
including
obesity
atherosclerosis.
This
review
will
summarize
what
is
known
common
obstacles
then
describe
recent
approaches
allowed
researchers
provide
a
more
complete
picture
functions
miRNA.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Март 17, 2023
Abstract
Chronic
kidney
disease
(CKD)
is
estimated
to
affect
10–14%
of
global
population.
Kidney
fibrosis,
characterized
by
excessive
extracellular
matrix
deposition
leading
scarring,
a
hallmark
manifestation
in
different
progressive
CKD;
However,
at
present
no
antifibrotic
therapies
against
CKD
exist.
fibrosis
identified
tubule
atrophy,
interstitial
chronic
inflammation
and
fibrogenesis,
glomerulosclerosis,
vascular
rarefaction.
Fibrotic
niche,
where
organ
initiates,
complex
interplay
between
injured
parenchyma
(like
tubular
cells)
multiple
non-parenchymal
cell
lineages
(immune
mesenchymal
located
spatially
within
scarring
areas.
Although
the
mechanisms
are
complicated
due
kinds
cells
involved,
with
help
single-cell
technology,
many
key
questions
have
been
explored,
such
as
what
kind
renal
tubules
profibrotic,
myofibroblasts
originate,
which
immune
how
communicate
each
other.
In
addition,
genetics
epigenetics
deeper
that
regulate
fibrosis.
And
reversible
nature
epigenetic
changes
including
DNA
methylation,
RNA
interference,
chromatin
remodeling,
gives
an
opportunity
stop
or
reverse
therapeutic
strategies.
More
marketed
(e.g.,
RAS
blockage,
SGLT2
inhibitors)
developed
delay
progression
recent
years.
Furthermore,
better
understanding
also
favored
discover
biomarkers
fibrotic
injury.
review,
we
update
advances
mechanism
summarize
novel
treatment
for
CKD.
Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Июнь 9, 2022
Abstract
Chronic
kidney
disease
(CKD)
is
a
chronic
renal
dysfunction
syndrome
that
characterized
by
nephron
loss,
inflammation,
myofibroblasts
activation,
and
extracellular
matrix
(ECM)
deposition.
Lipotoxicity
oxidative
stress
are
the
driving
force
for
loss
of
including
tubules,
glomerulus,
endothelium.
NLRP3
inflammasome
signaling,
MAPK
PI3K/Akt
RAAS
signaling
involves
in
lipotoxicity.
The
upregulated
Nox
expression
decreased
Nrf2
result
directly.
injured
resident
cells
release
proinflammatory
cytokines
chemokines
to
recruit
immune
such
as
macrophages
from
bone
marrow.
NF-κB
JAK-STAT
Toll-like
receptor
cGAS-STING
major
pathways
mediate
inflammation
inflammatory
cells.
produce
secret
great
number
profibrotic
TGF-β1,
Wnt
ligands,
angiotensin
II.
TGF-β
Notch
evoke
activation
promote
generation
ECM.
potential
therapies
targeted
these
also
introduced
here.
In
this
review,
we
update
key
lipotoxicity,
stress,
kidneys
with
injury,
drugs
based
on
latest
studies.
Unifying
will
be
instrumental
advance
further
basic
clinical
investigation
CKD.
Biomedicine & Pharmacotherapy,
Год журнала:
2021,
Номер
143, С. 112132 - 112132
Опубликована: Сен. 1, 2021
Fibrosis
is
the
endpoint
of
pathological
remodeling.
This
process
contributes
to
pathogenesis
several
chronic
disorders
and
aging-associated
organ
damage.
Different
molecular
cascades
contribute
this
process.
TGF-β,
WNT,
YAP/TAZ
signaling
pathways
have
prominent
roles
in
A
number
long
non-coding
RNAs
microRNAs
been
found
regulate
fibrosis
through
modulation
activity
related
pathways.
miR-144-3p,
miR-451,
miR-200b,
miR-328
are
among
that
participate
pathology
cardiac
fibrosis.
Meanwhile,
miR-34a,
miR-17-5p,
miR-122,
miR-146a,
miR-350
liver
different
situations.
PVT1,
MALAT1,
GAS5,
NRON,
PFL,
MIAT,
HULC,
ANRIL,
H19
We
review
impact
aging-related
pathologies.
Frontiers in Physiology,
Год журнала:
2020,
Номер
11
Опубликована: Июль 9, 2020
Renal
proximal
tubular
cells
are
high
energy-demanding
mainly
relying
on
fatty
acid
oxidation.
In
stress
conditions,
such
as
transient
hypoxia,
oxidation
(FAO)
decreases
and
carbohydrate
catabolism
fails
to
compensate
for
the
energy
demand.
this
scenario,
surviving
exhibit
peculiar
phenotype
associating
with
fibrosis
that
is
histological
manifestation
of
a
process
culminating
in
chronic
end-stage
kidney
disease.
Genome-wide
transcriptome
analysis
revealed
that,
together
inflammation,
FAO
top
dysregulated
pathway
diseases
lowered
expression
key
enzymes
regulators.
Another
evidence
links
derangement
progressive
decrease
peroxisome
proliferator-activated
receptor
α
(PPARα),
master
regulator
enzymes,
aged
people
triggers
age-associated
renal
fibrosis.
To
allow
FAO,
coordinate
network
transport
proteins
required.
Indeed,
mitochondrial
inner
membrane
impermeable
acyl-CoAs
specialized
system,
well
known
carnitine
shuttle,
needed
translocate
acids
moieties,
conjugated
carnitine,
into
matrix
β-oxidation.
The
first
component
system
palmitoyltransferase
1
(CPT1)
responsible
transfer
acyl
moieties
carnitine.
Several
studies
indicated
stimulation
CPT1
activity
has
protective
effect
against
Therefore,
transporters
linked
may
represent
potential
pharmacological
targets
deserving
further
attention
development
new
drugs
attenuate
dysfunction.
Antioxidants,
Год журнала:
2022,
Номер
11(7), С. 1356 - 1356
Опубликована: Июль 12, 2022
Acute
kidney
injury
(AKI)
and
chronic
disease
(CKD)
are
interconnected
conditions,
CKD
is
projected
to
become
the
fifth
leading
global
cause
of
death
by
2040.
New
therapeutic
approaches
needed.
Mitochondrial
dysfunction
oxidative
stress
have
emerged
as
drivers
in
acute
settings,
promoting
AKI-to-CKD
transition.
In
this
work,
we
review
role
mitochondrial
AKI
progression
discuss
novel
approaches.
Specifically,
evidence
for
diverse
models
(nephrotoxicity,
cytokine
storm,
ischemia-reperfusion
injury)
(diabetic
disease,
glomerulopathies)
discussed;
clinical
implications
information
on
key
mitochondria-related
transcriptional
regulators
peroxisome
proliferator-activated
receptor
gamma
coactivator
1-alpha,
transcription
factor
EB
(PGC-1α,
TFEB),
carnitine
palmitoyl-transferase
1A
(CPT1A)
addressed;
current
status
development
targeting
mitochondria
updated;
barriers
mitochondria-targeted
interventions
discussed,
including
lack
diagnostic
tests
that
allow
us
categorize
baseline
renal
dysfunction/mitochondrial
monitor
its
response
intervention.
Finally,
milestones
further
research
proposed.
Cells,
Год журнала:
2021,
Номер
10(3), С. 541 - 541
Опубликована: Март 4, 2021
The
delivery
of
cancer
therapeutics
can
be
limited
by
pharmacological
issues
such
as
poor
bioavailability
and
high
toxicity
to
healthy
tissue.
pH-low
insertion
peptides
(pHLIPs)
represent
a
promising
tool
overcome
these
limitations.
pHLIPs
allow
for
the
selective
agents
tumors
on
basis
pH,
taking
advantage
acidity
hypoxic
tumor
microenvironment.
This
review
article
highlights
various
applications
in
which
have
been
utilized
targeting
treating
diseases
environments,
including
small
molecule
inhibitors,
toxins,
nucleic
acid
analogs,
fluorescent
dyes,
nanoparticles.