Unlocking the power of empagliflozin: Rescuing inflammation in hyperglycaemia‐ exposed human cardiomyocytes through comprehensive multi‐level analysis
European Journal of Heart Failure,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 14, 2025
Aims
Hyperglycaemic
conditions
increase
cardiac
stress,
a
common
phenomenon
associated
with
inflammation,
aging,
and
metabolic
imbalance.
Sodium–glucose
cotransporter
2
inhibitors,
class
of
anti‐diabetic
drugs,
showed
to
improve
cardiovascular
functions
although
their
mechanism
action
has
not
yet
been
fully
established.
This
study
investigated
the
effects
empagliflozin
on
cardiomyocytes
following
high
glucose
exposure,
specifically
focusing
inflammatory
responses.
Methods
results
A
three‐part
strategy
was
formulated:
(i)
meta‐analysis
selected
randomized
clinical
trials
carried
out
assess
anti‐inflammatory
in
diabetic
patients;
(ii)
impact
human
cardiomyocyte
AC16
cells
exposed
normal
(5
mM)
(33
concentrations
for
7
days
explored
by
evaluating
gene
expression
protein
levels
pivotal
markers
endoplasmic
reticulum
damage,
calcium
modulation;
(iii)
silico
data
from
bioinformatic
analyses
were
exploited
construct
an
interaction
map
delineating
potential
tissue.
Empagliflozin
reversed
high‐glucose
mediated
alterations
at
transcriptional
level,
decreasing
inflammatory,
metabolic,
aging
signatures.
Specifically,
vitro
experiments
cardiomyocytes,
meta‐analyses
biomarkers
peripheral
blood
samples,
sequencing
pathological
heart
tissues,
all
support
that
exerts
both
systemically
directly
tissue,
cardiomyocytes.
Conclusion
Our
provides
insights
based
robust
mechanistic
optimizing
failure
management
highlights
intricate
interplay
between
diabetes,
health.
Язык: Английский
Myeloid-Derived Suppressor Cells (MDSCs) and Obesity-Induced Inflammation in Type 2 Diabetes
Diagnostics,
Год журнала:
2024,
Номер
14(21), С. 2453 - 2453
Опубликована: Ноя. 1, 2024
Type
2
diabetes
mellitus
is
a
complex
metabolic
disorder
characterized
by
insulin
resistance
and,
subsequently,
decreased
secretion.
This
condition
closely
linked
to
obesity,
major
risk
factor
that
boosts
the
development
of
chronic
systemic
inflammation,
which,
in
turn,
recognized
for
its
crucial
role
onset
resistance.
Under
conditions
adipose
tissue,
particularly
visceral
fat,
becomes
an
active
endocrine
organ
releases
wide
range
pro-inflammatory
mediators,
including
cytokines,
chemokines,
and
adipokines.
These
along
with
cluster
differentiation
(CD)
markers,
contribute
maintenance
low-grade
promote
cellular
signaling
facilitate
infiltration
inflammatory
cells
into
tissues.
Emerging
studies
have
indicated
accumulation
new
cell
population
tissue
these
conditions,
known
as
myeloid-derived
suppressor
(MDSCs).
possess
ability
suppress
immune
system,
impacting
obesity-related
inflammation.
Given
limited
literature
addressing
MDSCs
context
type
diabetes,
this
article
aims
explore
interaction
between
MDSC
activity.
Identifying
understanding
immature
essential
not
only
improving
management
but
also
potential
targeted
therapeutic
strategies
aimed
at
both
glycemic
control
reduction
associated
Язык: Английский
The synergistic role of gut microbiota and RNA in metabolic diseases: mechanisms and therapeutic insights
Frontiers in Microbiology,
Год журнала:
2025,
Номер
16
Опубликована: Янв. 29, 2025
The
gut
microbiota
plays
a
pivotal
role
in
human
metabolic
health
by
influencing
immune
responses,
digestion,
and
homeostasis.
Recent
research
highlights
the
intricate
interactions
between
RNA,
especially
non-coding
RNAs,
regulating
processes.
Dysbiosis
of
has
been
linked
to
disorders
such
as
type
2
diabetes,
obesity,
metabolic-associated
fatty
liver
disease
(MAFLD)
heart
disease.
Microbial
metabolites,
including
short-chain
acids
(SCFAs),
modulate
RNA
expression,
lipid
metabolism,
glucose
regulation,
inflammatory
responses.
Additionally,
microRNAs
(miRNAs)
long
RNAs
(lncRNAs)
serve
critical
regulators
these
processes,
with
emerging
evidence
showing
that
gut-derived
metabolites
affect
post-transcriptional
gene
regulation.
This
review
synthesizes
current
understanding
microbiota-RNA
axis
its
diseases.
By
exploring
molecular
mechanisms,
particularly
how
microbiota-derived
signals
pathways,
underscores
potential
targeting
this
for
therapeutic
interventions.
Furthermore,
it
examines
dysbiosis
leads
epigenetic
changes
m6A
methylation,
contributing
pathogenesis.
These
insights
offer
new
perspective
on
prevention
treatment
diseases,
applications
personalized
medicine.
Язык: Английский
Clinical metabolomics in type 2 diabetes mellitus: from pathogenesis to biomarkers
Chuanxin Liu,
Haoqiang Chen,
Yujin Ma
и другие.
Frontiers in Endocrinology,
Год журнала:
2025,
Номер
16
Опубликована: Фев. 25, 2025
As
a
multidimensional
metabolic
disorder,
the
disability
and
death
rate
of
type
2
diabetes
mellitus
(T2DM)
has
increased
over
time.
T2DM
covers
wide
range
pathological
manifestations
ranging
from
hyperglycemia
to
multi-organ
failure,
it
potential
evolve
into
acute
complications,
including
ketosis
chronic
complications
such
as
peripheral
neuropathy,
retinopathy,
nephropathy.
mainly
occurs
in
microvascular
large
vessels
thus
is
restricted
for
clinician
diagnose
prescribe.
However,
mechanism
clinical
diagnosis
are
inadequate.
High-throughput
metabolomics,
characterized
by
non-invasive
diagnostic
techniques
identify
biomarkers
distinct
stages
T2DM,
been
increasingly
recognized
vigorous
tool
with
latent
capacity
translation.
The
stratification
can
significantly
reduce
mortality
rates.
By
tracing
metabolome
associated
pathways
impaired
fasting
blood
glucose
or
tolerance
severe
organ
chief
contributions
large,
independent
population-based
cohorts
summarized
herein.
These
results
facilitate
understanding
pathophysiology
supports
research
accurate
diagnosis,
risk
prediction,
curative
effect,
stages,
prognosis
judgment
T2DM.
Язык: Английский
Dysregulated inflammation, oxidative stress, and protein quality control in diabetic HFpEF: unraveling mechanisms and therapeutic targets
Simin Delalat,
Innas Sultana,
Hersh Osman
и другие.
Cardiovascular Diabetology,
Год журнала:
2025,
Номер
24(1)
Опубликована: Май 14, 2025
Abstract
Background
Type
2
diabetes
mellitus
(T2DM)
represents
a
significant
risk
factor
for
cardiovascular
disease,
particularly
heart
failure
with
preserved
ejection
fraction
(HFpEF).
HFpEF
predominantly
affects
elderly
individuals
and
women,
is
characterized
by
dysfunctions
associated
metabolic,
inflammatory,
oxidative
stress
pathways.
Despite
being
the
most
prevalent
phenotype
in
patients
T2DM,
its
underlying
pathophysiological
mechanisms
remain
inadequately
elucidated.
Objective
This
study
aims
to
investigate
effects
of
on
myocardial
inflammation,
stress,
protein
quality
control
(PQC)
HFpEF,
particular
emphasis
insulin
signaling,
autophagy,
chaperone-mediated
responses.
Methods
We
conducted
an
analysis
left
ventricular
tissue
from
patients,
both
without
diabetes,
employing
range
molecular,
biochemical,
functional
assays.
The
passive
stiffness
cardiomyocytes
(Fpassive)
was
assessed
demembranated
before
after
implementing
treatments
aimed
at
reducing
inflammation
(IL-6
inhibition),
(Mito-TEMPO),
enhancing
PQC
(HSP27,
HSP70).
Inflammatory
markers
(NF-κB,
IL-6,
TNF-α,
ICAM-1,
VCAM-1,
NLRP3),
(ROS,
GSH/GSSG
ratio,
lipid
peroxidation),
components
signaling
pathways
(PI3K/AKT/mTOR,
AMPK,
MAPK,
PKG)
were
evaluated
using
western
blotting,
immunofluorescence,
ELISA
techniques.
Results
Hearts
diabetic
exhibited
significantly
heightened
upregulation
NF-κB,
NLRP3
inflammasome.
increase
accompanied
elevated
diminished
nitric
oxide
(NO)
bioavailability,
impaired
activation
NO-sGC-cGMP-PKG
pathway.
Notably,
dysregulation
observed,
as
indicated
decreased
AKT
phosphorylation
autophagy
regulation
mediated
AMPK
mTOR.
Additionally,
dysfunction
evidenced
reduced
expression
levels
HSP27
HSP70,
which
correlated
increased
cardiomyocyte
stiffness.
Targeted
therapeutic
interventions
effectively
Fpassive,
IL-6
inhibition,
Mito-TEMPO,
HSP
administration
leading
improvements
mechanical
properties.
Conclusion
findings
this
elucidate
mechanistic
relationship
among
impairment
context
HFpEF.
Therapeutic
strategies
that
target
these
dysregulated
pathways,
including
mitochondrial
antioxidants,
protection,
may
enhance
function
T2DM.
Addressing
molecular
could
facilitate
development
novel
specifically
tailored
population.
Graphical
abstract
Язык: Английский
Restoration of vascular dysfunction resulting from maternal high-fat diet via modulation of the NLRP3/IL-1β axis
Clinical and Experimental Hypertension,
Год журнала:
2024,
Номер
47(1)
Опубликована: Дек. 26, 2024
This
study
investigated
the
impact
of
maternal
high-fat
diet
on
vascular
function
and
endothelial
homeostasis
in
offspring.
We
found
that
offspring
exposed
to
exhibited
elevated
blood
pressure,
impaired
abdominal
aortic
function,
imbalance.
These
changes
were
accompanied
by
increased
levels
reactive
oxygen
species
(ROS)
upregulation
pro-inflammatory
cytokines
(including
IL-1β,
TNF-α,
IL-6,
IL-10).
Treatment
with
NLRP3
or
IL-1β
inhibitors
prevented
deterioration
reduced
NO
production,
inflammation
induced
exposure
compared
control
group.
The
findings
suggest
during
pregnancy,
mitigating
impairments
can
be
achieved
inhibiting
NLRP3/IL-1β
pathway.
Язык: Английский
Exploring the role of NLRP3 infalmmasome in diabetes: a literature review and bibliometric analysis
Frontiers in Endocrinology,
Год журнала:
2024,
Номер
15
Опубликована: Дек. 9, 2024
Diabetes
has
emerged
as
the
foremost
public
health
challenge
of
21st
century,
with
a
notable
shift
towards
managing
it
through
an
inflammatory
lens.
This
study
seeks
to
investigate
role
NLRP3
infalmmasome
in
diabetes
over
past
ten
years,
leveraging
bibliometric
analysis
pinpoint
prevailing
trends,
underscore
critical
focal
points,
and
establish
roadmap
for
subsequent
research
endeavors.
Язык: Английский