Background
Oral
carcinoma
presents
a
significant
health
challenge,
prompting
the
need
for
innovative
therapeutic
approaches.
Elevation
of
inflammatory
mediators,
including
tumor
necrosis
factor-alpha
(TNF-α)
and
interleukin-6
(IL-6),
has
promoted
cellular
proliferation,
inhibited
apoptosis,
fostered
oral
cancer
progression
through
complex
signaling
pathways.
Hesperidin,
flavanone
glycoside
found
in
citrus
fruits,
is
keen
interest
this
study
as
it
been
proven
to
have
multiple
benefits
vivo
vitro
studies.
However,
mechanism
behind
anticancer
activity
hesperidin
remains
obscure.
Aim
The
aimed
explore
potential
on
human
cells
(KB
cells)
by
modulating
pro-inflammatory
apoptotic
mechanisms.
Methods
Cancer
cell
growth
inhibitory
was
assessed
using
MTT
(3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium
Bromide)
assay.
Gene
expression
analysis
performed
real-time
RT-PCR
analysis.
In
addition,
silico
docking
conducted
confirm
binding
affinity
with
apoptosis
molecules.
data
were
analyzed
one-way
ANOVA
"t"
test.
Results
Utilizing
assay,
dose-dependent
cytotoxic
effect
unveiled,
remarkable
IC50
value
indicative
its
potent
inhibition
proliferation.
Complementing
these
findings
(p<0.05),
qRT-PCR
demonstrated
hesperidin's
regulatory
influence
key
molecular
targets
within
KB
line.
Hesperidin
treatment
resulted
noteworthy
reduction
TNF-α,
interleukin-1
beta
(IL-1-β),
IL-6,
nuclear
factor
kappa-light-chain-enhancer
activated
B
(NF-κB),
B-cell
lymphoma
2
(Bcl-2)
mRNA
levels
highlighting
role
migration,
inflammation
processes.
Simultaneously,
BAX
indicating
an
enhancement
death.
Molecular
simulations
further
revealed
robust
affinities
between
target
proteins,
suggesting
disrupt
functions
pathways
cells.
Conclusion
effects
line
anti-inflammatory
properties
position
compelling
candidate
exploration
quest
effective
treatments.
These
shed
light
intricate
mechanisms
underlying
promise
agent
against
carcinoma.
Naunyn-Schmiedeberg s Archives of Pharmacology,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 14, 2025
Abstract
Doxorubicin
(DOX)
is
a
highly
potent
broad-spectrum
anticancer
drug,
but
it
has
severe
side
effects,
including
hepatotoxicity.
Therefore,
we
evaluated
the
efficacy
of
febuxostat
(FBX),
specific
inhibitor
xanthine
oxidase
and
antioxidant,
in
blocking
hepatotoxicity
associated
with
DOX
rats.
Rats
were
treated
FBX
(10
or
15
mg/kg/day
orally
for
2
weeks)
given
(15
mg/kg
as
single
dose
at
7th
day,
intraperitoneal)
to
induce
The
results
indicated
that
could
reduce
pathological
alterations
liver
tissues
induced
by
ameliorate
inappropriate
changes
function
biomarkers
(AST,
ALT,
ALP)
serum,
oxidative
stress
parameters
(catalase,
superoxide
dismutase,
NOX1,
NQO-1,
HO-1,
Keap-1,
Nrf2)
inflammatory
markers
(NF-κB
p65,
TNF-α,
NLRP3).
Additionally,
attenuated
p53,
BAX,
cytochrome
C,
caspase-9,
caspase-3
levels
restrain
cell
apoptosis.
In
addition,
therapy
was
found
increase
protein
SIRT-1
AMPK
liver.
These
findings
demonstrate
can
caused
rats
through
mechanisms
counteract
stress,
inflammation,
Matrix
metalloproteinase-9
(MMP-9),
total
superoxide
dismutase
(T-SOD)
and
sirtuin
(SIRT)-1
are
interrelated
molecules
linked
with
oxidative
stress
periodontitis
pathogenesis
which
may
have
implications
for
both
the
diagnosis
of
or
efficacy
periodontal
treatment.
This
study
aimed
to
evaluate
salivary
serum
MMP-9,
T-SOD,
SIRT-1
levels
in
stage
3
patients
(P-S3)
following
non-surgical
treatment
(NSPT).
Forty-nine
subjects,
comprising
17
healthy,
16
P-S3
Grade
B
(P-S3GB),
C
(P-S3GC)
participated
study.
Clinical
parameters,
T-SOD
were
evaluated
at
baseline
from
all
participants
3-months
patients.
Enzyme-linked
immunosorbent
assay
(ELISA)
was
used
assess
biochemical
parameters.
All
clinical
parameters
improved
groups
(p
<
0.05)
after
NSPT.
In
P-S3GB
GC
groups,
MMP-9
higher
than
healthy
controls
decreased
NSPT
0.05).
P-S3GC
group
had
ones
Salivary
similar
among
>
After
NSPT,
only
group,
decreased,
increased
showed
positive
correlations
The
results
suggest
that
potential
biomarkers
diagnosing
evaluating
However,
further
research
is
necessary
validate
these
findings
across
grades
stages
periodontitis.
retrospectively
registered
on
13/02/2024
trials.gov
number
NCT06255470.
Immunopharmacology and Immunotoxicology,
Год журнала:
2025,
Номер
unknown, С. 1 - 10
Опубликована: Март 25, 2025
This
study
aimed
to
investigate
the
possible
protective
effect
of
roflumilast
(RFL)
on
cyclophosphamide
(CP)-induced
ovarian
toxicity
as
well
underlying
mechanism.
Female
Wistar
rats
received
vehicle
(n
=
6)
or
CP
(200
mg/kg,
i.p.).
The
other
2
groups
6
for
each)
were
orally
pretreated
with
RFL
at
dosages
0.5
and
1
respectively,
14
days
then
after
one
hour
administration
14th
day,
intraperitoneally
administered
a
single
dose
CP.
Serum
tissue
samples
collected.
Biochemical,
real-time
polymerase
chain
reaction,
histopathological
immunohistopathological
examination
carried
out.
significantly
elevated
serum
follicle-stimulating
hormone
(FSH)
luteinizing
(LH)
compared
group.
remarkably
contents
Sirtuin-1
(SIRT1),
heme
oxygenase-1
(HO-1),
reduced
nuclear
factor-kappa
B
(NF-ĸb)
p65/NF-ĸB
ratio
control
Compared
group,
Nrf2
gene
expression,
malondialdehyde
(MDA),
glutathione
(GSH)
content.
It
also
protein
expression
TNF-α
caspase-3.
can
be
concluded
that
(0.5
mg/kg)
protected
against
CP-induced
via
altering
SIRT1/Nrf2/NF-ĸB
pathway,
ameliorating
changes
in
addition
its
anti-apoptotic
effect.
Cardiology and Cardiovascular Medicine,
Год журнала:
2024,
Номер
08(01)
Опубликована: Янв. 1, 2024
Hypercholesterolemia
is
a
major
risk
factor
for
atherosclerosis
as
oxidized-low-density
lipoproteins
(ox-LDL)
contribute
to
the
formation
of
foam
cells
and
inflammation.
Increased
immune
cell
infiltration
oxidative
stress
induce
instability
plaque.
Rupture
unstable
plaque
precipitates
adverse
ischemic
events.
Since
reactive
oxygen
species
(ROS)
play
critical
role
in
vulnerability,
regulating
ROS
generation
may
have
therapeutic
potential.
Sirtuins,
specifically
sirtuin-3
(SIRT3),
are
antigenic
molecules
that
can
reduce
by
reducing
mitochondrial
production
through
epigenetic
modulation.
Lack
SIRT3
expression
associated
with
dysregulation
endothelial
function
following
high-fat
high-cholesterol
diet.
deacetylates
FOXO3a
(Forkhead
transcription
O
subfamily
member
3a)
protects
mitochondria
against
which
lead
even
further
protective
anti-oxidizing
properties.
This
study
was
designed
investigate
association
between
hyperlipidemia,
intimal
injury,
chronic
inflammation,
NAD-dependent
deacetylase
SIRT-3,
FOXO3,
antioxidant
genes,
carotid
arteries
hypercholesterolemic
Yucatan
microswine.
We
found
injury
state
led
increased
stress,
neointimal
hyperplasia,
size
while
decreasing
anti-oxidative
regulatory
genes
mediators.
The
findings
suggest
targeting
SIRT3-FOXO3aoxidative
pathway
will
significance.
Frontiers in Endocrinology,
Год журнала:
2024,
Номер
15
Опубликована: Май 16, 2024
Background
It
is
well
known
that
metabolic
disorders,
including
type
1
diabetes
(T1D),
are
often
associated
with
reduced
male
fertility,
mainly
increasing
oxidative
stress
and
impairing
the
hypothalamus–pituitary–testis
(HPT)
axis,
consequently
altered
spermatogenesis
sperm
parameters.
Herein,
using
a
rat
model
of
T1D
obtained
by
treatment
streptozotocin
(STZ),
we
analyzed
several
parameters
testicular
activity.
Methods
A
total
10
adult
Wistar
rats
were
divided
into
two
groups
five:
control
T1D,
single
intraperitoneal
injection
STZ.
After
3
months,
anesthetized
sacrificed;
one
testis
was
stored
at
-80°C
for
biochemical
analysis,
other
fixed
histological
immunofluorescence
analysis.
Results
The
data
confirmed
induced
and,
consequently,
alterations
in
both
somatic
germ
cells.
This
aspect
highlighted
enhanced
apoptosis,
steroidogenesis
Leydig
cell
maturity,
impaired
spermatogenesis.
In
addition,
blood–testis
barrier
integrity
compromised,
as
shown
levels
structural
proteins
(N-cadherin,
ZO-1,
occludin,
connexin
43,
VANGL2)
phosphorylation
status
regulative
kinases
(Src
FAK).
Mechanistically,
dysregulation
SIRT1/NRF2/MAPKs
signaling
pathways
proven,
particularly
nuclear
translocation
NRF2,
affecting
its
ability
to
induce
transcription
genes
encoding
antioxidant
enzymes.
Finally,
stimulation
inflammation
pyroptosis
also
confirmed,
increased
some
markers,
such
NF-κB
NLRP3.
Conclusion
combined
allowed
us
confirm
has
detrimental
effects
on
Moreover,
better
comprehension
molecular
mechanisms
underlying
association
between
disorders
fertility
could
help
identify
novel
targets
prevent
treat
related
T1D.
Experimental Gerontology,
Год журнала:
2023,
Номер
174, С. 112137 - 112137
Опубликована: Март 9, 2023
The
strong
interest
shown
in
the
study
of
causes
aging
recent
decades
has
uncovered
many
mechanisms
that
could
contribute
to
rate
aging.
These
include
mitochondrial
ROS
production,
DNA
modification
and
repair,
lipid
peroxidation-induced
membrane
fatty
acid
unsaturation,
autophagy,
telomere
shortening
rate,
apoptosis,
proteostasis,
senescent
cells,
most
likely
there
are
others
waiting
be
discovered.
However,
all
these
well-known
work
only
or
mainly
at
cellular
level.
Although
it
is
known
organs
within
a
single
individual
do
not
age
exactly
same
well-defined
species
longevity.
Therefore,
loose
coordination
among
different
cells
tissues
needed
ensure
lifespan.
In
this
article
we
focus
on
less
extracellular,
systemic,
whole
organism
level
loosely
coordinate
keep
margins
its
We
discuss
heterochronic
parabiosis
experiments,
systemic
factors
distributed
through
vascular
system
like
DAMPs,
fragments,
TF-like
proteins,
inflammaging,
as
well
epigenetic
proposed
clocks
situated
levels
organization
from
brain.
interorgan
systems
can
help
determine
longevity
further
adaptation
ecosystem.
International Journal of Environmental Research and Public Health,
Год журнала:
2022,
Номер
19(21), С. 14536 - 14536
Опубликована: Ноя. 5, 2022
Metabolic
syndrome
(MetS)
prevalence
continues
to
climb
significantly
worldwide
in
today’s
ad
libitum
society.
MetS
has
tremendous
societal
and
economic
ramifications,
making
it
imperative
develop
effective
strategies
for
preventing
controlling
alleviate
this
growing
burden.
Periodontal
disease
are
associated
with
several
risk
factors.
Studies
the
past
have
demonstrated
that
obesity,
cardiovascular
illness,
type
2
diabetes
mellitus
a
negative
effect
on
severity
of
periodontal
disease.
Patients
metabolic
elevated
serum
levels
proinflammatory
mediators
such
as
tumor
necrosis
factor-alpha
interleukin-6
C-reactive
protein.
Similar
inflammatory
mediators,
interleukin-6,
factor-alpha,
protein,
increased
patients
severe
Remarkably,
intermittent
fasting
is
underpinned
by
scientific
evidence,
claiming
be
most
non-pharmacological,
potential
therapeutic
alternative
combating
wide
range
metabolic,
inflammatory,
lifestyle-related
diseases.
Nonetheless,
an
insufficient
investigation
been
performed
determine
whether
benefits
inflammation
Here,
we
show
interrelationship
between
contextualize
beneficial
impact
modulating
chronic
response.
We
also
anticipate
review
paves
way
further
exploration
unique
research
paradigm
representing
cost-effective
strategy
conventional
management
diseases
which
may
serve
foundation
integrative
vision
relevant
primary,
diagnostic,
purposes.
Cell Proliferation,
Год журнала:
2023,
Номер
57(1)
Опубликована: Июль 26, 2023
Abstract
Dental
pulp
injury
remains
a
clinical
challenge
with
limited
therapeutic
approaches.
In
the
present
study,
we
sought
to
prove
that
dental
stromal
cells
(DPSCs)
mitochondrial
transfer
could
promote
repair
and
endoplasmic
reticulum
(ER)‐mitochondrial
contacts
have
significant
regulatory
effect
on
transfer.
Healthy
DPSCs
were
co‐cultured
directly
or
indirectly
injured
in
first
molar
of
1–2
month
SD
rats
vitro.
Mitochondrial
was
observed
after
24
h
co‐culture
using
fluorescence
microscopy
live
cell
workstation.
After
for
1W,
8‐OhdG
immunofluorescence,
membrane
potential
total
oxidant
status/total
antioxidant
status
used
detect
function
before
Subsequently,
mitochondria‐ER
co‐transfer
regulated
by
modulating
binding
healthy
DPSCs,
results
GRP78
CHOP
PDI
immunofluorescence
haematoxylin
eosin
staining
tissue
analysed
clarify
effects
stress
(ERS),
repair.
Fluorescence
workstation
showed
between
DPSCs.
Meanwhile,
significantly
restored
By
mitochondrial‐ER
binding,
efficiency
affected
had
an
impact
ERS
cells.
promotes
pulpal
functional
recovery
damaged
is
binding.