Trends in Molecular Medicine,
Год журнала:
2023,
Номер
29(5), С. 354 - 363
Опубликована: Март 22, 2023
Adolescent
polycystic
ovary
syndrome
(PCOS)
is
a
highly
prevalent,
reversible,
endocrine-metabolic
mode
essentially
driven
by
ectopic
fat,
which,
in
turn,
often
results
from
mismatch
between
early
adipogenesis
and
later
lipogenesis,
or
prenatal
postnatal
weight
gain.
The
key
features
of
adolescent
PCOS
are
menstrual
irregularity
androgen
excess
(hirsutism,
acne,
and/or
high
testosterone).
frequently
preceded
rapid
maturation
(early
variants
adrenarche/pubarche
puberty/menarche,
also
accelerated
fat)
diagnosed
2
8
years
after
menarche,
thus
during
late
adolescence
adulthood.
Treatment
should
not
only
focus
on
symptoms,
but
reduce
the
amount
thereby
aiming
for
an
overall
state
preconception
health.
Endocrine Reviews,
Год журнала:
2020,
Номер
42(1), С. 77 - 96
Опубликована: Сен. 8, 2020
Metformin
is
a
first-line
therapy
for
the
treatment
of
type
2
diabetes,
due
to
its
robust
glucose-lowering
effects,
well-established
safety
profile,
and
relatively
low
cost.
While
metformin
has
been
shown
have
pleotropic
effects
on
glucose
metabolism,
there
general
consensus
that
major
effect
in
patients
with
diabetes
mostly
mediated
through
inhibition
hepatic
gluconeogenesis.
However,
despite
decades
research,
mechanism
by
which
inhibits
this
process
still
highly
debated.
A
key
reason
these
discrepant
likely
inconsistency
dosage
across
studies.
Widely
studied
mechanisms
action,
such
as
complex
I
leading
AMPK
activation,
only
observed
context
supra-pharmacological
(>1
mM)
concentrations,
do
not
occur
clinical
setting.
Thus,
challenged
recent
years
new
proposed.
Based
observation
alters
cellular
redox
balance,
redox-dependent
action
described
several
groups.
Recent
studies
clinically
relevant
(50-100
μM)
concentrations
inhibit
gluconeogenesis
substrate-selective
manner
both
vitro
vivo,
supporting
action.
Here,
we
review
current
literature
regarding
metformin's
molecular
Frontiers in Immunology,
Год журнала:
2020,
Номер
11
Опубликована: Май 19, 2020
Growth/differentiation
factor-15
(GDF-15),
also
named
macrophage
inhibitory
cytokine-1,
is
a
divergent
member
of
the
transforming
growth
factor
β
superfamily.
While
physiological
expression
barely
detectable
in
most
somatic
tissues
humans,
GDF-15
abundant
placenta.
Elsewhere,
often
induced
under
stress
conditions,
seemingly
to
maintain
cell
and
tissue
homeostasis;
however,
moderate
increase
blood
levels
observed
with
age.
Highly
elevated
are
mostly
linked
pathological
conditions
including
inflammation,
myocardial
ischemia,
notably
cancer.
has
thus
been
widely
explored
as
biomarker
for
disease
prognosis.
Mechanistically,
induction
anorexia
via
brainstem-restricted
receptor
GFRAL
(glial
cell-derived
neurotrophic
[GDNF]
family
α-like)
well
documented.
have
become
attractive
targets
metabolic
intervention.
Still,
several
mediated
effects
(including
its
role
pregnancy)
difficult
explain
described
pathway.
Hence,
there
clear
need
better
understand
non-metabolic
GDF-15.
With
particular
emphasis
on
immunomodulatory
potential
this
review
discusses
roles
pregnancy
infarction,
autoimmune
disease,
specifically
Importantly,
strong
predictive
value
may
plausibly
be
immune-regulatory
function.
The
associations
mechanistic
data
support
hypothesis
that
acts
immune
checkpoint
an
emerging
target
cancer
immunotherapy.
Journal of Clinical Investigation,
Год журнала:
2020,
Номер
130(10), С. 5074 - 5087
Опубликована: Сен. 1, 2020
Hypoxia-inducible
factors
(HIFs)
and
the
HIF-dependent
cancer
hallmarks
angiogenesis
metabolic
rewiring
are
well-established
drivers
of
breast
aggressiveness,
therapy
resistance,
poor
prognosis.
Targeting
HIF
its
downstream
targets
in
metabolism
has
been
unsuccessful
so
far
clinical
setting,
with
major
unresolved
challenges
residing
target
selection,
development
robust
biomarkers
for
response
prediction,
understanding
harnessing
escape
mechanisms.
This
Review
discusses
pathophysiological
role
HIFs,
angiogenesis,
targeting
these
features
patients
cancer.
Rational
therapeutic
combinations,
especially
immunotherapy
endocrine
therapy,
seem
most
promising
exploitation
intricate
interplay
cells
tumor
microenvironment.
