Journal of Natural Products,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 28, 2025
Fourteen
new
indole
diterpenoids,
designated
as
asperdoles
A-N
(1-14),
were
isolated
from
the
endolichenic
fungus
Aspergillus
sp.
TJ403-YJ22.
Notably,
compounds
1-7
characterized
by
presence
of
2-keto-3-hydroxy-oxidized
moieties,
which
connected
to
diterpenoid
segments
via
methylene
bridges.
Compounds
1-5
featured
fused
6/6/6
ring
frameworks,
whereas
tetrahydropyran
in
6-14
was
cleaved,
resulting
formation
terminal
vicinal
diols
6-12
and
olefinic
double
bonds
13
14.
The
planar
structures
absolute
configurations
these
elucidated
through
a
combination
NMR
spectroscopy,
HRESIMS,
Snatzke's
method,
single-crystal
X-ray
diffraction
analysis,
ECD
calculations.
Compound
4
exhibited
selective
FXR
agonistic
activity,
with
an
EC50
value
4.1
±
0.3
μM,
suggesting
its
potential
therapeutic
application
treatment
cholestasis.
Cell Death Discovery,
Год журнала:
2024,
Номер
10(1)
Опубликована: Окт. 10, 2024
Diabetes
mellitus
is
a
metabolic
disorder
with
persistent
hyperglycemia
caused
by
variety
of
underlying
factors.
Chronic
can
lead
to
diverse
serious
consequences
and
diversified
complications,
which
pose
threat
patients.
Among
the
major
complications
are
cardiovascular
disease,
kidney
diabetic
foot
ulcers,
retinopathy,
neurological
disorders.
Heme
oxygenase
1
(HO-1)
protective
enzyme
antioxidant,
anti-inflammatory
anti-apoptotic
effects,
has
been
intensively
studied
plays
an
important
role
in
complications.
By
inducing
expression
activity
HO-1,
it
enhance
anti-inflammatory,
capacity
tissues,
thus
reduce
degree
damage
The
present
study
aims
review
relationship
between
HO-1
pathogenesis
diabetes
its
involved
regulation
macrophage
polarization
promotes
M1
state
(pro-inflammatory)
towards
M2
(anti-inflammatory).
Induction
dendritic
cells
inhibits
them
maturation
secretion
pro-inflammatory
cytokines
regulatory
T
cell
(T
Biology,
Год журнала:
2024,
Номер
13(8), С. 597 - 597
Опубликована: Авг. 8, 2024
Diabetic
nephropathy
(DN)
is
one
of
the
common
complications
diabetes
and
main
cause
end-stage
renal
disease
(ESRD)
in
clinical
practice.
Schisandrin
A
(Sch
A)
has
multiple
pharmacological
activities,
including
inhibiting
fibrosis,
reducing
apoptosis
oxidative
stress,
regulating
immunity,
but
its
mechanism
for
treatment
DN
still
unclear.
In
vivo,
streptozotocin
(STZ)
a
high-fat
diet
were
used
to
induce
type
2
diabetic
rats,
Sch
was
administered
4
weeks.
At
same
time,
protein–protein
interaction
(PPI)
networks
established
analyze
overlapping
genes
A.
Subsequently,
Kyoto
Encyclopedia
Genes
Genomes
(KEGG)
Gene
Ontology
(GO)
analyses
performed
determine
hub
pathway.
addition,
molecular
docking
preliminarily
verify
affinity
proteins
Further,
H&E
staining,
Sirius
red
immunohistochemistry,
immunofluorescence,
western
blot
analysis
detect
location
expression
related
DN.
This
study
revealed
multi-target
multi-pathway
characteristics
First,
could
effectively
improve
glucose
tolerance,
reduce
urine
microprotein
creatinine
levels,
alleviate
pathological
damage
rats.
Second,
EGFR
gene
screened
(43)
(100)
(2524).
Finally,
it
that
inhibit
protein
levels
PTRF
reduced
apoptosis-related
proteins,
this
effect
modulation
AKT/GSK-3β
signaling
summary,
protective
may
be
potential
therapeutic
target,
throughout
modulating
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(16), С. 9035 - 9035
Опубликована: Авг. 20, 2024
Cell
deaths
maintain
the
normal
function
of
tissues
and
organs.
In
pathological
conditions,
abnormal
activation
or
disruption
cell
death
often
leads
to
pathophysiological
effects.
Diabetic
kidney
disease
(DKD),
a
significant
microvascular
complication
diabetes,
is
linked
high
mortality
morbidity
rates,
imposing
substantial
burden
on
global
healthcare
systems
economies.
Loss
detachment
podocytes
are
key
changes
in
progression
DKD.
This
review
explores
potential
mechanisms
apoptosis,
necrosis,
autophagy,
pyroptosis,
ferroptosis,
cuproptosis,
podoptosis
podocytes,
focusing
how
different
modes
contribute
It
recognizes
limitations
current
research
presents
latest
basic
clinical
studies
targeting
podocyte
pathways
Lastly,
it
focuses
future
treat
DKD,
with
intention
inspiring
further
development
therapeutic
strategies.
Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 8, 2025
Abstract
Background
Diabetic
nephropathy
(DN)
is
one
of
the
most
frequent
complications
diabetes
mellitus.
Since
early
diagnosis
DN
crucial
to
prevent
progression
disease
towards
renal
failure,
many
efforts
have
been
made
in
recent
years
introduce
new
diagnostic
biomarkers.
Recent
studies
suggest
that
non-coding
RNAs
could
act
as
a
novel
biomarker
for
detection
and
prediction
progress.
Accordingly,
current
study
we
investigated
expression
levels
miR-155
CTBP1-AS2
type
2
(T2D),
patients
control
subjects
evaluated
their
potential
DN.
Method
A
total
189
age
sex-matched
including
65
T2D
with
normo-albuminuria,
61
who
had
history
albuminuria,
63
were
included
this
case-control
study.
The
determined
using
QRT-PCR.
Results
results
revealed
level
was
significantly
reduced
patients.
In
addition,
higher
macroalbuminuria
compared
microalbuminuria
normo-albuminuria.
without
proteinuria
than
macroalbuminuria.
also
showed
there
significant
positive
correlation
between
DBP,
TG,
TC,
SCr
and,
BUN
negative
HDL-C
eGFR
values.
Conclusion
Deregulation
may
represent
useful
biomarkers
European Journal of Therapeutics,
Год журнала:
2025,
Номер
31(1), С. 1 - 10
Опубликована: Фев. 28, 2025
Objective:
Diabetic
nephropathy
(DN)
is
one
of
the
most
serious
microvascular
complications
Diabetes
Mellitus,
prevalence
and
mortality
which
are
increasing.
Recently,
microRNAs
(miRNAs)
used
in
pathogenesis
diagnosis
many
diseases
have
been
identified.
In
this
study
investigate
relationship
between
albuminuria
miRNA
levels
patients
with
type
2
diabetes
mellitus
(T2DM)
treated
dapagliflozin,
to
elucidate
potential
nephroprotective
effects
dapagliflozin
through
modulation.
Methods:
This
retrospective
included
47
T2DM
(25
male,
22
female)
diabetic
dapagliflozin.
Blood
samples
were
collected
at
baseline
(day
0)
after
approximately
60
days
treatment.
Levels
miRNA-21,
miRNA-141,
miRNA-377
analyzed
using
real-time
PCR.
Clinical
laboratory
parameters,
including
glucose,
HbA1c,
urine
albumin
protein
levels,
also
assessed.
Statistical
analysis
Wilcoxon
signed-rank
test
Spearman's
rank
correlation
test.
Results:
Significant
decreases
observed
urinary
protein,
treatment
(p<0.01).
decreased
significantly
following
A
positive
was
found
day
0
serum
glucose
levels.
negative
miRNA-21
HbA1c
No
significant
correlations
or
Conclusion:
Dapagliflozin
DN
associated
reductions
alongside
improvements
glycemic
control
renal
function
markers.
These
findings
suggest
that
may
exert
its
partly
modulation
DN-associated
miRNAs.
be
a
therapeutic
option
treat
an
effective
strategy
prevent
kidney
damage.
Further
research
warranted
mechanisms
underlying
these
explore
miRNAs
as
biomarkers
targets
management.
Background:
Hepatic
ischemia-reperfusion
injury
(HIRI)
significantly
affects
the
prognosis
of
liver
surgery,
such
as
hepatocellular
carcinoma
resection
and
transplantation.
However,
pathogenesis
HIRI
has
not
been
fully
elucidated,
prevention
treatment
strategies
remain
challenging.
Methods:
A
mouse
model
was
established,
schisandrin
B
(Sch
B)
used
to
intervene
in
HIRI.
The
effect
Sch
on
assessed
using
hematoxylin
eosin
(HE)
staining,
quantitative
polymerase
chain
reaction
(qPCR),
Western
blot
(WB),
immunohistochemistry,
enzyme-linked
immunosorbent
assay
(ELISA).
Results:
expression
alanine
aminotransferase
(ALT)
aspartate
(AST)
serum
increased,
indicating
successful
construction
model.
In
intervention
group,
ALT
AST
levels
were
decreased.
Hematoxylin
staining
qPCR
results
demonstrated
that
could
reduce
mice.
immunohistochemistry
showed
reduced
mice
by
decreasing
autophagy-related
factors
Beclin-1
LC3-II.
Conclusions:
Additionally,
immunohistochemical
indicated
(Beclin-1
LC3-II)
hepatocyte
damage-related
(caspase-3,
caspase-9,
Bax),
thereby
reducing
electron
microscopy,
confirmed
autophagy
alleviate
MiR-181b-5p
plays
a
critical
role
in
the
pyroptosis
and
injury
of
kidney
tubular
cells
diabetic
disease
(DKD).
The
long
noncoding
RNA
(lncRNA)
small
nucleolar
hostgene
7
(SNHG7)
has
been
shown
to
bind
inhibit
function
miR-181b-5p.
However,
precise
SNHG7
DKD
remains
unclear.
To
address
this,
current
study
measured
expression
levels
SNHG7,
miR-181b-5p,
Toll-like
receptor
4
(TLR4)
using
RT-qPCR
analysis
renal
biopsies
from
both
normal
individuals
patients
with
DKD.
An
vitro
model
was
subsequently
established
by
exposing
HK-2
high
glucose
(HG).
In
tissues
HG-stimulated
cells,
TLR4
were
significantly
elevated,
while
miR-181b-5p
markedly
reduced.
Knockdown
resulted
multiple
beneficial
effects:
it
effectively
attenuated
glucose-induced
lactate
dehydrogenase
(LDH)
leakage,
restored
cell
viability,
inhibited
production
inflammatory
cytokines
tumor
necrosis
factor
alpha
(TNF-α),
interleukin
18
(IL-18),
1β
(IL-1β),
suppressed
activation
nucleotide-binding
oligomerization
domain
(NOD)-like
pyrin
containing
3
(NLRP3)/acysteinyl
aspartate-specific
proteinase
1
(caspase-1)/gasdermin
D
(GSDMD)
pathway.
Mechanistically,
functions
as
molecular
sponge
for
directly
targets
TLR4,
collectively
regulating
nuclear
factor-kappaB
(NF-κB)
pathway
activation.
Moreover,
inhibition
or
up-regulation
reversed
protective
effects
knockdown.
Additionally,
co-transfection
over-expression
vector
mimic
counteracted
overexpression
on
LDH
factors
pyroptosis-related
molecules.
summary,
acts
promoting
inflammation
DKD,
which
turn
regulates
NF-κB
signaling