Pharmaceuticals,
Journal Year:
2024,
Volume and Issue:
17(12), P. 1601 - 1601
Published: Nov. 27, 2024
Metformin
is
a
commonly
used
drug
for
treating
type
2
diabetes.
an
inexpensive
with
low/no
side
effects
and
well
tolerated
in
human
patients
of
different
ages.
Recent
therapeutic
strategies
disease
have
considered
the
benefits
repurposing.
This
includes
use
anti-diabetic
metformin.
Accordingly,
anti-inflammatory,
anti-cancer,
anti-viral,
neuroprotective,
cardioprotective
potentials
metformin
deemed
it
suitable
candidate
plethora
diseases.
As
results
from
preclinical
studies
using
cellular
animal
model
systems
appear
promising,
clinical
trials
context
non-diabetes-related
illnesses
been
started.
Here,
we
aim
to
provide
comprehensive
overview
potential
models
its
suggested
relationship
epigenetics
ailments
epigenetic
components.
Frontiers in Pharmacology,
Journal Year:
2022,
Volume and Issue:
13
Published: July 22, 2022
Objectives:
To
investigate
the
risk
of
varicocele,
erectile
dysfunction
(ED),
infertility,
prostatitis,
benign
prostate
hyperplasia
(BPH)
and
cancer
associated
with
metformin
use.
Materials
methods:
A
total
261,838
males,
mean
age
52.39
years
(SD:
11.39),
a
new-onset
type
2
diabetes
mellitus
in
1999-2009
were
identified
from
Taiwan's
National
Health
Insurance.
Among
them,
175,171
initiators
[metformin
(+)]
86,667
non-metformin
(-)]
initial
12-month
prescriptions
antidiabetic
drugs.
Follow-up
started
after
prescriptions.
Outcomes
followed
up
until
31
December
2011.
Intention-to-treat
(ITT)
per-protocol
(PP)
hazard
ratios
comparing
(+)
to
(-)
estimated
by
Cox
regression
incorporated
inverse
probability
treatment-weighting
using
propensity
scores.
Results:
The
median
follow-up
time
ranged
5.55-6.82
4.36-5.17
for
different
outcomes
ITT
analyses.
respective
PP
analyses
2.20-2.61
3.99-4.65
(+).
In
analyses,
(-),
incidence
rates
(per
100,000
person-years)
ED,
BPH
26.42,
455.89,
22.82,
590.23,
4226.19,
141.69,
respectively;
25.65,
488.10,
32.60,
510.30,
3685.66,
116.57.
(95%
confidence
intervals)
0.960
(0.784-1.174)
1.077
(1.026-1.130)
1.368
(1.116-1.676)
0.887
(0.849-0.927)
0.883
(0.868-0.899)
0.878
(0.802-0.961)
cancer.
0.845
(0.662-1.078),
1.350
(1.264-1.441),
1.396
(1.078-1.808),
0.800
(0.756-0.846),
0.875
(0.855-0.895),
0.613
(0.548-0.686).
Conclusion:
Metformin
use
patients
is
neutral
effect
on
higher
sexual
(ED
infertility)
reduced
prostate-related
health
(prostatitis,
cancer).
Frontiers in Endocrinology,
Journal Year:
2022,
Volume and Issue:
13
Published: Oct. 19, 2022
Metformin
is
the
first-line
oral
treatment
for
type
2
diabetes
mellitus
and
prescribed
to
more
than
150
million
people
worldwide.
Metformin's
effect
as
a
glucose-lowering
drug
well
documented
but
precise
mechanism
of
action
unknown.
A
recent
finding
an
association
between
paternal
metformin
increased
numbers
genital
birth
defects
in
sons
tendency
towards
skewed
secondary
sex
ratio
with
less
male
offspring
prompted
us
focus
on
other
evidence
reproductive
side
effects
this
drug.
humans
reduce
circulating
level
testosterone
both
men
women.
In
experimental
animal
models,
exposure
utero
induced
sex-specific
changes
adult
rat
reduced
fertility
manifested
30%
decrease
litter
size
fish,
intersex
testicular
tissue.
excreted
unchanged
into
urine
feces
present
wastewater
even
effluent
plants
from
where
it
spreads
rivers,
lakes,
drinking
water.
It
be
numerous
freshwater
samples
throughout
world
-
We
here
hypothesis
that
needs
considered
potential
toxicant
humans,
probably
also
wildlife.
There
urgent
need
studies
exploring
outcomes
animals,
aquatic
Frontiers in Oncology,
Journal Year:
2021,
Volume and Issue:
10
Published: Feb. 2, 2021
Metabolism
can
directly
drive
or
indirectly
enable
an
aberrant
chromatin
state
of
cancer
cells.
The
physiological
and
molecular
principles
the
metabolic
link
to
epigenetics
provide
a
basis
for
pharmacological
modulation
with
anti-diabetic
biguanide
metformin.
Here,
we
briefly
review
how
metabolite-derived
modifications
metabolo-epigenetic
machinery
itself
are
both
amenable
modification
by
metformin
in
local
systemic
manner.
First,
consider
capacity
target
global
pathways
specific
enzymes
producing
chromatin-modifying
metabolites.
Second,
examine
its
ability
fine-tune
activation
status
enzymes.
Third,
envision
interaction
between
metformin,
diet
gut
microbiota
might
systemically
regulate
inputs
chromatin.
Experimental
clinical
validation
metformin's
change
functional
outcomes
could
offer
proof-of-concept
therapeutically
test
adjustability
epigenomic
landscape
cancer.
Journal of Cancer,
Journal Year:
2022,
Volume and Issue:
13(6), P. 1859 - 1870
Published: Jan. 1, 2022
Objectives:
Metformin,
a
first-line
drug
that
has
been
used
for
type
2
diabetes
treatment,
recently
attracts
broad
attention
its
therapeutic
effects
on
diverse
human
cancers.
However,
effect
and
the
underlying
mechanisms
oral
squamous
cell
carcinoma
(OSCC)
are
not
well
known.
Materials
Methods:
OSCC
cells
were
to
evaluate
of
metformin
proliferation
colony
formation
in
vitro.
Tumor
assay
nude
mice
was
conducted
assess
vivo.
Western
blotting
immunohistochemistry
stain
performed
investigate
expression
acetylation
at
lysine
27
histone
H3
(H3K27ac)
methylation
(H3K27me3)
vitro
RNA-seq
ChIP-seq
explore
genome
profile
treatment
cells.
Results:
Metformin
inhibited
vitro,
as
growth
increased
global
H3K27ac
modification
Transcriptome
analysis
suggested
mainly
downregulated
pluripotency
stem
pathway,
development
involved
pathways
upregulated
cytokine
inflammatory
pathways.
Additionally,
transcription,
DNA
repair
replication
metformin-treated
Conclusions:
inhibits
concomitant
level
This
study
provides
insights
into
molecule
epigenome
basis
application
highlights
reprogrammed
cancer
regulation
epigenetic
modification.
Frontiers in Pharmacology,
Journal Year:
2022,
Volume and Issue:
13
Published: Aug. 8, 2022
A
target-based
drug
discovery
strategy
has
led
to
a
bias
away
from
low
molecular
weight
(MWT)
discovery.
Analysis
of
the
ACS
chemistry
registration
system
shows
that
most
MWT
drugs
were
first
made
in
time
era
before
Therapeutic
activity
among
was
identified
phenotypic
when
selected
based
on
their
effects
and
vitro
screening,
mechanism
action
considerations
experiences
with
fragment
screening
became
known.
The
common
perception
cannot
be
found
compounds
is
incorrect
both
history
our
own
experience
MLR-1023.
greater
proportion
are
commercially
available
compared
higher
factor
should
facilitate
biology
study.
We
posit
more
suited
identification
new
therapeutic
using
screens
provided
method
enough
capacity.
On-target
off-target
activities
discussed
perspective
because
concern
either
or
might
towards
promiscuous
combine
on-target
effects.
Among
ideal
repositioning
candidates
(late-stage
pre-clinical
clinically-experience
compounds),
pleiotropic
(multiple
actions)
far
likely
due
arising
where
single
target
mediates
multiple
benefits,
desirable
outcome
for
development
purposes
alternative.
Our
exemplar
compound,
MLR-1023,
discovered
by
subsequently
have
would
been
overlooked
current
medicinal
precedent.
diverse
described
this
compound
us,
others
arise
same
lyn
kinase
activation
target.
MLR-1023
serves
as
proof-of-principle
potent,
target,
can
screening.
Journal of Education Health and Sport,
Journal Year:
2021,
Volume and Issue:
11(9), P. 37 - 42
Published: Sept. 3, 2021
Introduction:
Life
expectancy
of
human
population
is
being
constantly
prolonged,
hence
there
a
lot
research
into
drug
that
will
prevent
the
effects
aging.
There
are
many
reports
metformin,
which
used
in
type
2
diabetes,
has
anti-aging
effects.
It
belongs
to
group
biguanides
and
been
since
1950s.
relatively
safe,
cheap
effective
drug,
makes
it
promising
subject
for
studies.
The
purpose
this
review
present
latest
developments
field.
Material
methods:
PubMed
scientific
base
was
searched
using
following
keywords:
aging,
anti-aging,
years
2017-2021.
Results:
Numerous
studies
show
metformin
an
impact
on
aging
through
nutrient
pathway,
AMPK
signaling
its
reactive
oxygen
species.
In
addition,
anti-cancer
effect,
inhibiting,
among
others,
rectal
cancer
cells
p53
mutant
colon
cancer.
Research
rodents
shown
organs,
including
CNS,
ovaries,
prostate,
heart
muscle
skin.
Conclusions:
Metformin,
most
commonly
oral
other
mechanisms
action.
Its
effect
works
organs
our
bodies,
gives
hope
find
substance.
However,
multicentre,
randomized
trials
needed
determine
exact
dose,
possible
side
effects,
various
organisms.
Archives of Medical Science,
Journal Year:
2023,
Volume and Issue:
unknown
Published: Jan. 20, 2023
Introduction
Metformin
(Met),
a
first-line
oral
anti-type
2
diabetes
medication
used
globally,
has
been
shown
to
hinder
cancer
progression
via
regulation
of
microRNAs
(miRNAs).
The
previous
reports
on
the
relationship
between
Met
use
and
risk
esophageal
squamous
cell
carcinoma
(ESCC)
have
controversial.
Hence,
this
study
aimed
explore
how
affected
ESCC
underlying
molecular
mechanism.
Material
methods
Cell
migration,
viability
invasiveness
were
respectively
investigated
using
wound
healing,
CCK-8
transwell
assay.
expressions
miR-141-3p
Sciellin
(SCEL)
mRNA
examined
by
mean
quantitative
real-time
PCR
(qRT-PCR)
assay,
SCEL
protein
level
was
quantified
western
blotting.
In
vivo
tests
performed
animals.
predicted
binding
more
evidenced
dual-luciferase
Results
treatment
in
largely
impaired
viability,
migration
invasiveness.
MiR-141-3p
showed
high
expression
downregulated
cells
after
treatment.
upregulation
Met-administered
restored
proliferative
ability,
also
attenuated
anti-tumor
effect
vivo.
targeted
whose
declined
ESCC,
reinforced
depleted
thus
partially
abolished
anti-cancer
impacts
Met-treated
cells.
Conclusions
restrains
regulating
miR-141-3p/SCEL
axis.
Our
findings
clearly
show
that
is
associated
with
lower
its
anticancer
could
potentially
be
treat
ESCC.
Research Square (Research Square),
Journal Year:
2023,
Volume and Issue:
unknown
Published: March 23, 2023
Abstract
Depression
is
considered
the
second
leading
cause
of
global
health
burden
after
cancer.
doubles
risk
metabolic
syndrome
in
overall
population.
Depressed
people
are
more
vulnerable
to
because
their
poor
health-related
practices.
The
regulatory
key
factors
between
diseases
and
depression
poorly
understood
terms
dysregulation
genes
affected
depressive
disorder.
We
employed
silico
analysis
quantitative
framework
understand
molecular
mechanism
its
related
diseases.
According
previous
studies,
regulator
tryptophan
metabolism,
IDO-1,
plays
an
important
role
pathophysiology
depression.
In
present
study,
docking
simulation
analyses
were
performed
determine
interaction
kinetics
Indoleamine
2,3-dioxygenase
(IDO-1)
with
drugs,
including
metformin,
pioglitazone
alpha-
tocopherol,
which
widely
used
treatment
diabetes
non-alcoholic
steatohepatitis
(NASH).
Our
study
aims
outline
effect
IDO1
on
hepatic
lipid
metabolism
vitro
vivo
.
found
that
stressed
mice
showed
improved
glucose
insulin
tolerance
compared
control
group.
IDO-1
expression
robustly
increased
serum
high-fat
diet-induced
mice.
confirms
knocked
down
aggravated
droplets
AML-12
hepatocytes
treated
free
fatty
acids
upregulated
mRNA
genes.
Hence,
may
contribute
a
significant
metabolism.
Taken
together,
our
findings
suggest
inhibit
accumulation
liver
can
serve
as
potent
drug
target
for
combat
abnormalities
along
stress
prevention.
