Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Окт. 14, 2024
Introduction
Diabetic
ketoacidosis
(DKA)
is
a
severe
and
potentially
fatal
acute
complication
in
diabetic
patients,
commonly
occurring
type
1
diabetes
(T1D)
but
also
seen
2
(T2D).
The
pathogenesis
of
DKA
involves
complex
physiological
processes
that
are
not
fully
understood,
especially
the
role
mitochondria.
Mitochondria,
known
as
powerhouse
cells,
plays
crucial
oxidative
phosphorylation
ATP
production,
which
vital
various
metabolic
diseases,
including
diabetes.
However,
exact
causal
relationship
between
mitochondrial
dysfunction
remains
unclear.
Methods
This
study
employed
Mendelian
randomization
(MR)
analysis
protein-protein
interaction
(PPI)
networks
to
systematically
explore
relationships
DNA
copy
number
(mtDNA-CN)
specific
proteins
with
DKA.
We
used
bidirectional
MR
genome-wide
association
(GWAS)
data
from
openGWAS
database
investigate
effects
mtDNA-CN
64
mitochondrial-related
on
its
subtypes
(T1DKA,
T2DKA,
unspecified-DKA).
Results
revealed
increased
significantly
reduces
risk
DKA,
whereas
effect
was
significant.
Mitochondrial-related
such
MRPL32,
MRPL33,
COX5B,
DNAJC19,
NDUFB8
showed
negative
indicating
their
potential
protective
roles.
Conversely,
ATP5F1B
COX4I2
have
positive
excessive
production
patients
may
be
detrimental
health
increase
complications
Discussion
results
emphasize
necessity
protecting
function
order
reduce
offers
novel
perspectives
molecular
pathways
involved
emphasizing
critical
functions
mt-DNA
distinct
proteins.
These
evidences
only
enhance
our
comprehension
implications
diabetes-related
identify
therapeutic
targets
for
individualized
treatment
approaches,
thereby
making
substantial
contribution
clinical
care
public
initiatives.
Phytomedicine,
Год журнала:
2024,
Номер
135, С. 156142 - 156142
Опубликована: Окт. 9, 2024
Diabetic
kidney
disease
(DKD)
is
one
of
the
most
common
microvascular
complications
in
patients
with
diabetes
mellitus.
In
this
condition,
renal
tubular
epithelial
mesenchymal
transition
(EMT)
an
important
factor
accelerating
progression
DKD
and
a
major
cause
fibrosis
end-stage
disease.
However,
therapeutic
effect
unsatisfactory
because
lack
effective
drugs.
Jia
Wei
Qingxin
Lotus
Seed
Drink
(QISD)
traditional
Chinese
medicine
compound
formula
that
has
shown
to
be
clinical
treatment
DKD.
potential
QISD
DKD-EMT
yet
fully
explored.
This
study
aimed
investigate
role
ameliorating
injury
its
mechanism.
The
active
ingredients
were
identified
via
ultra-performance
liquid
chromatography-mass
spectrometry/mass
spectrometry
(UHPLC-MS/MS).
A
mouse
model
was
constructed
by
high-fat
diet
feeding
intraperitoneal
injection
STZ
(60
mg/kg),
(14.46,
28.92,
57.84
g/kg/day)
administered
gavage
for
12
consecutive
weeks.
Dapagliflozin
(1
mg/kg/d)
used
as
positive
control.
Renal
pathological
damage
observed
HE,
PAS,
Masson
staining.
expression
levels
EMT-related
proteins
pathway
detected
immunohistochemistry,
RT-qPCR,
western
blot.
vitro
experiments,
EMT
induced
human
cells
(HK-2)
using
lipopolysaccharide
(LPS).
combination
CCK8
assay,
wound
healing
small-molecule
inhibitor
intervention,
overexpression
lentiviral
transfection
effects
on
cell
migration
ability,
adhesion
fibrotic
formation,
properties.
Animal
experiments
showed
improved
blood
glucose,
body
weight,
symptoms
excessive
drinking
eating,
mice,
reduced
extracellular
matrix
deposition,
delayed
injury,
inhibited
activation
histone
demethylase
JMJD1C.
UHPLC-MS/MS
molecular
docking
indicated
baicalin,
wogonoside,
oroxylin
A-7-O-β-D-glucuronide,
glulisine
found
could
bind
might
related
improvement
accompanied
reduction
SP1
ZEB1
expression.
not
only
reversed
JIB-04,
JMJD1C,
but
also
exacerbated
downstream
factors.
Thus,
affect
marker
E-cadherin
inhibiting
JMJD1C/SP1/ZEB1
signaling
pathway,
consequently
preventing
transformation
injury.
first
demonstrate
ameliorate
pathway.
These
findings
provide
strong
pharmacologic
evidence
use
Endocrine Connections,
Год журнала:
2023,
Номер
13(4)
Опубликована: Фев. 1, 2023
The
aim
of
this
study
was
to
investigate
the
relationship
between
weight-adjusted-waist
index
(WWI)
and
diabetic
kidney
disease
in
individuals
afflicted
with
type
2
diabetes.
