Metabolic dysfunction and insulin sensitizers in acute and chronic disease
Expert Opinion on Investigational Drugs,
Год журнала:
2025,
Номер
unknown, С. 1 - 10
Опубликована: Фев. 6, 2025
The
concept
of
insulin
resistance
has
been
a
major
topic
for
more
than
5
decades.
While
there
are
several
treatments
that
may
impact
resistance,
this
pathology
is
uniquely
addressed
by
mitochondrially
directed
thiazolidinedione
(TZD)
sensitizers.
Understanding
mechanism
action
and
consideration
'insulin
resistance'
as
consequence
metabolic
inflammation
allows
new
paradigm
approaching
chronic
diseases.
We
review
evolving
understanding
the
mitochondrial
pyruvate
carrier
(MPC)
TZD
sensitizers
discuss
how
reprogramming
metabolism
impacts
pleotropic
pharmacology
in
multiple
tissues.
Additional
lines
investigation
proposed.
A
change
can
facilitate
rethinking
clinical
trials,
specifically
beyond
treatment
frank
type
2
diabetes.
There
should
be
broader
evaluation
combination
with
weight
loss
lifestyle
approaches
across
diseases/syndromes
associated
resistance.
Finally,
'connecting
all
dots'
to
unwind
interconnectedness
cell
biology
involved
syndromes
impacted
dysfunction
efficacy
also
uncover
molecular
targets.
New
studies
discovery
development
novel
pharmacologic
agents.
Язык: Английский
Oxidative phosphorylation and breast cancer progression: insights into PGC-1α’s role in mitochondrial function
Naunyn-Schmiedeberg s Archives of Pharmacology,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 17, 2025
Язык: Английский
Immune Checkpoints Are New Therapeutic Targets in Regulating Cardio-, and Cerebro-Vascular Diseases and CD4+Foxp3+ Regulatory T Cell Immunosuppression
Ying Shao,
William Y. Yang,
Gayani Nanayakkara
и другие.
International Journal of Drug Discovery and Pharmacology,
Год журнала:
2024,
Номер
unknown, С. 100022 - 100022
Опубликована: Ноя. 26, 2024
Although
previous
reviews
explored
the
roles
of
selected
immune
checkpoints
(ICPs)
in
cardiovascular
diseases
(CVD)
and
cerebrovascular
from
various
perspectives,
many
related
aspects
have
yet
to
be
thoroughly
reviewed
analyzed.
Our
comprehensive
review
addresses
this
gap
by
discussing
cellular
functions
ICPs,
focusing
on
tissue-specific
microenvironment-localized
transcriptomic
posttranslational
regulation
ICP
expressions,
as
well
their
functional
interactions
with
metabolic
reprogramming.
We
also
analyze
how
14
pairs
including
CTLA-4/CD86-CD80,
PD1-PDL-1,
TIGIT-CD155,
regulate
CVD
pathogenesis.
Additionally,
covers
ICPs
modulating
CD4+Foxp3+
regulatory
T
cells
(Tregs),
cells,
innate
CVDs
diseases.
Furthermore,
we
outline
seven
immunological
principles
guide
development
new
ICP-based
therapies
for
CVDs.
This
timely
thorough
analysis
recent
advancements
challenges
provide
insights
into
role
CVDs,
Tregs,
will
support
novel
therapeutics
strategies
these
Язык: Английский
Perspective: Pathological transdifferentiation—a novel therapeutic target for cardiovascular diseases and chronic inflammation
Frontiers in Cardiovascular Medicine,
Год журнала:
2024,
Номер
11
Опубликована: Ноя. 26, 2024
Pathological
transdifferentiation,
where
differentiated
cells
aberrantly
transform
into
other
cell
types
that
exacerbate
disease
rather
than
promote
healing,
represents
a
novel
and
significant
concept.
This
perspective
discusses
its
role
potential
targeting
in
cardiovascular
diseases
chronic
inflammation.
Current
therapies
mainly
focus
on
mitigating
early
inflammatory
response
through
proinflammatory
cytokines
pathways
targeting,
including
corticosteroids,
TNF-α
inhibitors,
IL-1β
monoclonal
antibodies
blockers,
IL-6
nonsteroidal
anti-inflammatory
drugs
(NSAIDs),
along
with
modulating
innate
immune
memory
(trained
immunity).
However,
these
approaches
often
fail
to
address
long-term
tissue
damage
functional
regeneration.
For
instance,
fibroblasts
can
transdifferentiate
myofibroblasts
cardiac
fibrosis,
endothelial
may
undergo
mesenchymal
transition
(EndMT)
vascular
remodeling,
resulting
fibrosis
impaired
function.
Targeting
pathological
transdifferentiation
promising
therapeutic
avenue
by
focusing
key
signaling
drive
aberrant
cellular
phenotypic
transcriptomic
transitions.
approach
seeks
inhibit
or
modulate
plasticity
effective
regeneration
prevent
fibrosis.
Such
strategies
have
the
inflammation,
death,
damage,
providing
more
comprehensive
sustainable
treatment
solution.
Future
research
should
understanding
mechanisms
behind
identifying
relevant
biomarkers
master
regulators,
developing
preclinical
clinical
trials.
Integrating
new
existing
treatments
could
enhance
efficacy
improve
patient
outcomes.
Highlighting
as
target
paradigms,
leading
better
management
recovery
of
tissues
Язык: Английский