Hepatology,
Journal Year:
2023,
Volume and Issue:
78(5), P. 1625 - 1653
Published: Jan. 3, 2023
Liver
fibrosis
is
the
result
of
sustained
chronic
liver
injury
and
inflammation
leading
to
hepatocyte
cell
death
followed
by
formation
fibrous
scars,
which
hallmark
NASH
alcoholic
steatohepatitis
can
lead
cirrhosis,
HCC,
failure.
Although
progress
has
been
made
in
understanding
pathogenesis
clinical
consequences
hepatic
fibrosis,
therapeutic
strategies
for
this
disease
are
limited.
Preclinical
studies
suggest
that
peroxisome
proliferator-activated
receptor
alpha
plays
an
important
role
preventing
development
activating
genes
involved
detoxifying
lipotoxicity
toxins,
transrepressing
inflammation,
inhibiting
activation
stellate
cells.
Given
robust
preclinical
data,
several
agonists
have
tested
trials
fibrosis.
Here,
we
provide
update
on
recent
mechanisms
prevents
discuss
potential
targeting
PPARα
antifibrotic
treatments.
Diabetes & Metabolism Journal,
Journal Year:
2022,
Volume and Issue:
46(4), P. 517 - 532
Published: July 28, 2022
Statins
are
the
cornerstone
of
prevention
and
treatment
atherosclerotic
cardiovascular
disease
(ASCVD).
However,
even
under
optimal
statin
therapy,
a
significant
residual
ASCVD
risk
remains.
Therefore,
there
has
been
an
unmet
clinical
need
for
novel
lipid-lowering
agents
that
can
target
low-density
lipoprotein
cholesterol
(LDL-C)
other
atherogenic
particles.
During
past
decade,
several
drugs
have
developed
dyslipidemia.
Inclisiran,
small
interfering
RNA
targets
proprotein
convertase
subtilisin/kexin
type
9
(PCSK9),
shows
comparable
effects
to
PCSK9
monoclonal
antibodies.
Bempedoic
acid,
ATP
citrate
lyase
inhibitor,
is
valuable
option
patients
with
intolerance.
Pemafibrate,
first
selective
peroxisome
proliferator-activated
receptor
alpha
modulator,
showed
favorable
benefit-risk
balance
in
phase
2
trial,
but
large
3
trial
(PROMINENT)
was
recently
stopped
futility
based
on
late
interim
analysis.
High
dose
icosapent
ethyl,
modified
eicosapentaenoic
acid
preparation,
benefits.
Evinacumab,
angiopoietin-like
(ANGPTL3)
antibody,
reduces
plasma
LDL-C
levels
refractory
hypercholesterolemia.
Novel
antisense
oligonucleotides
targeting
apolipoprotein
C3
(apoC3),
ANGPTL3,
lipoprotein(a)
significantly
attenuated
their
molecules
beneficial
associated
dyslipidemias.
Apolipoprotein
A1
(apoA1)
considered
as
potential
exploit
athero-protective
high-density
(HDL-C),
solid
evidence
necessary.
In
this
review,
we
discuss
mode
action
outcomes
these
beyond
statins.
Terapevticheskii arkhiv,
Journal Year:
2022,
Volume and Issue:
94(2), P. 216 - 253
Published: Feb. 15, 2022
The
National
Consensus
was
prepared
with
the
participation
of
Medical
Association
for
Study
Multimorbidity,
Russian
Scientific
Liver
Society,
Endocrinologists,
Gerontologists
and
Geriatricians,
Society
Preventive
Cardiology,
Professional
Foundation
Promotion
Medicine
Fund
PROFMEDFORUM.
aim
multidisciplinary
consensus
is
a
detailed
analysis
course
non-alcoholic
fatty
liver
disease
(NAFLD)
main
associated
conditions.
definition
NAFLD
given,
its
prevalence
described,
methods
diagnosing
components
such
as
steatosis,
inflammation
fibrosis
are
described.
association
number
cardio-metabolic
diseases
(arterial
hypertension,
atherosclerosis,
thrombotic
complications,
type
2
diabetes
mellitus,
obesity,
dyslipidemia,
etc.),
chronic
kidney
risk
developing
hepatocellular
cancer
were
analyzed.
review
non-drug
treatment
modern
opportunities
pharmacotherapy
presented.
possibilities
new
molecules
in
considered:
agonists
nuclear
receptors,
antagonists
pro-inflammatory
molecules,
etc.
positive
properties
disadvantages
currently
used
drugs
(vitamin
E,
thiazolidinediones,
etc.)
Special
attention
paid
to
multi-target
ursodeoxycholic
acid
molecule
complex
multifactorial
disease.
Its
anti-inflammatory,
anti-oxidant
cytoprotective
properties,
ability
reduce
steatosis
an
independent
factor
development
cardiovascular
pathology,
hepatic
through
modulation
autophagy
considered.
influence
glucose
lipid
homeostasis
have
anticarcinogenic
effect
has
been
demonstrated.
statement
advanced
provisions
practitioners
optimize
diagnosis
related
common
pathogenetic
links
diseases.
Biomolecules,
Journal Year:
2023,
Volume and Issue:
13(8), P. 1264 - 1264
Published: Aug. 18, 2023
The
number
of
patients
with
nonalcoholic
fatty
liver
disease
(NAFLD)/nonalcoholic
steatohepatitis
(NASH)
is
increasing
globally
and
raising
serious
concerns
regarding
the
medical
economic
burden
incurred
for
their
treatment.
progression
NASH
to
more
severe
conditions
such
as
cirrhosis
hepatocellular
carcinoma
requires
transplantation
avoid
death.
Therefore,
therapeutic
intervention
required
in
stage,
although
no
drugs
are
currently
available
this.
Several
anti-NASH
candidate
have
been
developed
that
enable
treatment
via
modulation
distinct
signaling
cascades
include
a
series
targeting
peroxisome
proliferator-activated
receptor
(PPAR)
subtypes
(PPARα/δ/γ)
considered
be
attractive
because
they
can
regulate
both
systemic
lipid
metabolism
inflammation.
Multiple
PPAR
dual/pan
agonists
but
only
few
them
evaluated
clinical
trials
NAFLD/NASH.
Herein,
we
review
current
trial
status
future
prospects
PPAR-targeted
treating
In
addition,
summarize
our
recent
findings
on
binding
modes
potencies/efficacies
several
estimate
potentials
against
NASH.
Considering
development
numerous
has
abandoned
side
effects,
also
propose
repositioning
already
approved,
safety-proven
Frontiers in Cardiovascular Medicine,
Journal Year:
2024,
Volume and Issue:
11
Published: Aug. 7, 2024
Historically,
atherosclerotic
cardiovascular
disease
(ASCVD)
risk
profile
mitigation
has
had
a
predominant
focus
on
low
density
lipoprotein
cholesterol
(LDL-C).
In
this
narrative
review
we
explore
the
residual
ASCVD
beyond
LDL-C
with
hypertriglyceridaemia,
recent
clinical
trials
of
therapeutics
targeting
hypertriglyceridaemia
and
novel
modalities
addressing
other
factors.
Biomedical Chromatography,
Journal Year:
2025,
Volume and Issue:
39(3)
Published: Feb. 7, 2025
This
research
study
presents
a
precise,
accurate,
and
linear
liquid-chromatography
method
for
the
determination
of
pemafibrate
in
tablet
dosage
forms,
despite
presence
high
volume
excipients.
Various
challenges
were
addressed
through
experimental
approaches
evidence-based
solutions.
The
employs
suitable
stationary
phase,
X-Bridge
C18
(150
×
4.6
mm,
3.5
μm),
an
appropriate
isocratic
program.
Key
parameters
include
flow
rate
1.0
mL/min,
column
temperature
40°C,
injection
10
μL,
runtime
15
min.
wavelength
was
set
at
210
nm
because
its
response.
Mobile
phase
optimization,
based
on
results,
consists
0.1%
H3PO4
buffer
acetonitrile
40:60
v/v
ratio.
has
been
validated
according
to
ICH
Q2
(R2)
Ch.
P
<9101>
guidelines,
achieving
recovery
99.1%
100.5%
levels
50%,
100%,
150%.
Linearity
demonstrated
from
25%
300%
concentration
levels,
with
correlation
coefficient
(r2)
value
1.000.
Precision
results
showed
%RSD
values
1.1.
Forced
degradation
studies
indicated
sensitivity
acid
hydrolysis
stress
conditions
stability
under
physical
conditions.
iScience,
Journal Year:
2020,
Volume and Issue:
23(11), P. 101727 - 101727
Published: Oct. 23, 2020
Most
triacylglycerol-lowering
fibrates
have
been
developed
in
the
1960s-1980s
before
their
molecular
target,
peroxisome
proliferator-activated
receptor
alpha
(PPARα),
was
identified.
Twenty-one
ligand-bound
PPARα
structures
deposited
Protein
Data
Bank
since
2001;
however,
binding
modes
of
and
physiological
ligands
remain
unknown.
Here
we
show
thirty-four
X-ray
crystallographic
ligand-binding
domain,
which
are
composed
a
"Center"
four
"Arm"
regions,
complexes
with
five
endogenous
fatty
acids,
six
clinical
use,
synthetic
agonists.
High-resolution
structural
analyses,
combination
coactivator
recruitment
thermostability
assays,
demonstrate
that
stearic
palmitic
acids
presumably
ligands;
coordination
to
Arm
III
is
important
for
high
potency/selectivity
pemafibrate
GW7647;
agonistic
activities
enhanced
by
partial
agonist
GW9662.
These
results
renew
our
understanding
ligand
recognition
contribute
design
next-generation
PPAR-targeted
drugs.
Frontiers in Cardiovascular Medicine,
Journal Year:
2021,
Volume and Issue:
8
Published: April 29, 2021
Postprandial
lipemia
plays
an
important
role
in
the
formation,
occurrence,
and
development
of
atherosclerosis,
it
is
closely
related
to
coronary
heart
disease
other
diseases
involving
endothelial
dysfunction,
oxidative
stress,
inflammation,
mechanisms.
Therefore,
has
become
a
focus
area
for
further
research.
The
studies
on
postprandial
mainly
include
TG,
TRL,
VLDL,
CM,
remnant
cholesterol.
Diurnal
triglyceride
patterns
hyperlipidemia
are
very
relevant
now
insufficiently
covered.
possible
mechanisms
between
cardiovascular
have
been
reviewed
this
article
by
referring
literature
recent
years.
research
progress
effects
function,
inflammation
highlighted.
intervention
discussed.
Non-medicinal
such
as
diet
exercise
improves
lipemia.
As
medicinal
intervention,
statin,
fibrate,
ezetimibe,
omega-3
fatty
acids,
niacin
found
improve
lipid
levels.
Novel
medications
pemafibrate,
PCSK9,
apoCIII
inhibitors
Gut
microbiota
metabolism,
some
indicated
that
intestinal
microorganisms
may
affect
metabolism
environmental
factors.
Whether
gut
can
reduce
lipemia,
therefore
against
AS,
be
worthy
study.
