International Journal of Molecular Sciences,
Год журнала:
2021,
Номер
22(11), С. 6112 - 6112
Опубликована: Июнь 6, 2021
Skin
cancers
are
growing
in
incidence
worldwide
and
primarily
caused
by
exposures
to
ultraviolet
(UV)
wavelengths
of
sunlight.
UV
radiation
induces
the
formation
photoproducts
other
lesions
DNA
that
if
not
removed
repair
may
lead
mutagenesis
carcinogenesis.
Though
factors
cause
skin
carcinogenesis
reasonably
well
understood,
studies
over
past
10-15
years
have
linked
timing
exposure
implicate
a
role
for
body's
circadian
clock
response
disease
risk.
Here
we
review
what
is
known
about
clock,
how
it
affects
various
aspects
physiology,
affect
rhythms
skin.
Furthermore,
molecular
understanding
has
led
development
small
molecules
target
proteins;
thus,
discuss
potential
use
such
compounds
manipulating
clock-controlled
processes
modulate
responses
mitigate
cancer
Cellular and Molecular Gastroenterology and Hepatology,
Год журнала:
2021,
Номер
12(5), С. 1847 - 1872.e0
Опубликована: Янв. 1, 2021
Circadian
rhythms
are
daily
physiological
oscillations
driven
by
the
circadian
clock:
a
24-hour
transcriptional
timekeeper
that
regulates
hormones,
inflammation,
and
metabolism.
known
to
be
important
for
health,
but
whether
their
loss
contributes
colorectal
cancer
is
not
known.
We
tested
nonredundant
clock
gene
Bmal1
in
intestinal
homeostasis
tumorigenesis,
using
Apcmin
model
of
cancer.Bmal1
mutant,
epithelium-conditional
photoperiod
(day/night
cycle)
disrupted
mice
bearing
allele
were
assessed
tumorigenesis.
Tumors
normal
nontransformed
tissue
characterized.
Intestinal
organoids
transcription
RNA
sequencing,
vivo
organoid
assays
used
test
Bmal1-dependent
proliferation
self-renewal.Loss
or
increases
tumor
initiation.
In
epithelium
transcripts
involved
regeneration
stem
cell
signaling.
have
no
self-autonomous
function
only
weak
vivo.
clock-disrupted
tumors
show
high
Yes-associated
protein
1
(Hippo
signaling)
activity
low
Wnt
(Wingless
Int-1)
activity.
self-renewal
1-dependent
manner.Bmal1
pathways,
including
Hippo
signaling,
potentiates
Transcript
profiling:
GEO
accession
number:
GSE157357.
Journal of Pineal Research,
Год журнала:
2022,
Номер
73(1)
Опубликована: Апрель 18, 2022
Circadian
rhythm
disruption
(CRD)
represents
a
major
contributor
to
tumor
proliferation.
Nonetheless,
the
role
of
CRD
in
clinical
prediction
cancer
outcomes
has
not
been
well
studied.
In
this
study,
we
developed
computational
algorithm,
which
was
implemented
an
open-source
R
package
CRDscore,
define
intratumoral
status
circadian
three
representative
single-cell
RNA-seq
data
sets
lung
adenocarcinoma.
We
found
that
malignant
cells
with
high
CRDscore
were
characterized
by
activation
glycolysis
and
epithelial-mesenchymal
transition
pathways.
Furthermore,
cell
communication
analysis
indicated
played
pivotal
T
exhaustion,
may
be
responsible
for
poor
prognosis
malignancy.
then
validated
findings
public
bulk
transcriptome
datasets
involving
22
types.
Cox
regression
revealed
valuable
prognostic
biomarker.
A
model
containing
23
circadian-related
genes
performed
predicting
immunotherapeutic
14
independent
cohorts.
Importantly,
decreased
detect
RNA
sequencing
on
H1299
melatonin
treatment.
Meanwhile,
downregulated
expression
level
SNAIL
TWIST,
contributed
invasive
phenotype.
conclusion,
study
provides
novel
framework
characterizing
using
transcriptomic
further
confirmed
molecular
mechanisms
underlying
metabolic
reprogramming
exhaustion
under
CRD.
The
better
understanding
provide
new
possibilities
incorporating
"anticancer
approaches
based
clocks"
into
treatment
protocols
precision
medicine.
Abstract
Bmal1
(Brain
and
muscle
arnt-like,
or
Arntl)
is
a
bHLH/PAS
domain
transcription
factor
central
to
the
transcription/translation
feedback
loop
of
biologic
clock.
Although
well-established
as
major
regulator
circadian
rhythm,
growing
number
studies
in
recent
years
have
shown
that
dysfunction
underlies
variety
psychiatric,
neurodegenerative-like,
endocrine
metabolism-related
disorders,
well
potential
oncogenic
roles.
In
this
review,
we
systematically
summarized
expression
different
brain
regions,
its
neurological
functions
related
not
rhythm
biological
clock,
pathological
phenotypes
arising
from
knockout.
This
review
also
discusses
oscillation
rhythmicity,
especially
suprachiasmatic
nucleus,
provides
perspective
on
future
progress
research.
Trends in Pharmacological Sciences,
Год журнала:
2023,
Номер
44(10), С. 689 - 704
Опубликована: Авг. 28, 2023
Mood
disorders
account
for
a
significant
global
disease
burden,
and
pharmacological
innovation
is
needed
as
existing
medications
are
suboptimal.
A
wide
range
of
evidence
implicates
circadian
sleep
dysfunction
in
the
pathogenesis
mood
disorders,
there
growing
interest
these
chronobiological
pathways
focus
treatment
innovation.
We
review
contemporary
three
promising
areas
circadian-clock-based
therapeutics
disorders:
targeting
system
informed
by
mechanistic
molecular
advances;
time-tailoring
medications;
personalizing
using
parameters.
also
consider
limitations
challenges
accelerating
development
new
circadian-informed
pharmacotherapies
disorders.
Nature Reviews Molecular Cell Biology,
Год журнала:
2020,
Номер
21(9), С. 494 - 495
Опубликована: Июль 22, 2020
Circadian
clocks
control
the
function
of
our
immune
system,
virus
replication
and
severity
infections.
Our
daily
rhythms
also
regulate
pharmacokinetics
efficacy
several
therapeutics.
Consequently,
better
understanding
effects
circadian
biology
on
SARS-CoV-2
infection
would
improve
clinical
management
COVID-19.
infections
pharmacokinetics.
Ray
Reddy
argue
that
COVID-19
management.
iScience,
Год журнала:
2021,
Номер
24(4), С. 102335 - 102335
Опубликована: Март 20, 2021
Time
of
eating
synchronizes
circadian
rhythms
metabolism
and
physiology.
Inverted
feeding
can
uncouple
peripheral
clocks
from
the
central
clock
located
in
suprachiasmatic
nucleus.
However,
system-wide
changes
physiology
entrained
to
inverted
tissues
remain
largely
unexplored.
Here,
we
performed
a
24-h
global
profiling
transcripts
metabolites
mouse
study
transition
kinetics
during
feeding,
revealed
distinct
phase
entrainment
diurnal
transcriptomes
by
which
graded
fat
tissue
(near-completely
entrained),
liver,
kidney,
heart.
Phase
tracked
with
those
were
gated
light-related
cues.
Integrated
analysis
demonstrated
that
fatty
acid
oxidation
completely
heart
despite
slow
kinetics/resistance
feeding.
This
multi-omics
resource
defines
signatures
(www.CircaMetDB.org.cn).
Circadian
rhythm
disruption
(CD)
is
associated
with
impaired
glucose
homeostasis
and
type
2
diabetes
mellitus
(T2DM).
While
the
link
between
CD
T2DM
remains
unclear,
there
accumulating
evidence
that
of
fasting/feeding
cycles
mediates
metabolic
dysfunction.
Here,
we
used
an
approach
encompassing
analysis
behavioral,
physiological,
transcriptomic,
epigenomic
effects
consequences
restoring
through
time-restricted
feeding
(tRF)
in
mice.
Results
show
perturbs
pancreatic
β
cell
function
loss
circadian
transcriptional
epigenetic
identity.
In
contrast,
restoration
cycle
prevented
CD-mediated
dysfunction
by
reestablishing
regulation
tolerance,
function,
profile,
reestablishment
proline
acidic
amino
acid–rich
basic
leucine
zipper
(PAR
bZIP)
transcription
factor
DBP
expression/activity.
This
study
provides
mechanistic
insights
into
corresponding
beneficial
tRF
prevention
T2DM.
Abstract
With
the
aging
world
population,
prevalence
of
aging‐related
disorders
is
on
rise.
Diseases
such
as
Alzheimer's,
type
2
diabetes
mellitus
(T2DM),
Parkinson's,
atherosclerosis,
hypertension,
and
osteoarthritis
are
age‐related,
most
these
diseases
comorbidities
or
risk
factors
for
AD;
however,
our
understandings
molecular
events
that
regulate
occurrence
still
not
fully
understood.
Brain
muscle
Arnt‐like
protein‐1
(Bmal1)
an
irreplaceable
clock
gene
governs
multiple
important
physiological
processes.
Continuous
research
Bmal1
in
AD
associated
ongoing,
this
review
picks
relevant
studies
a
detailed
account
its
role
mechanisms
diseases.
Oxidative
stress
inflammation
turned
out
to
be
common
by
which
deficiency
promotes
diseases,
other
Bmal1‐dependent
remain
identified.
Promising
therapeutic
strategies
involved
regulation
provided,
including
melatonin,
natural
compounds,
metformin,
d‐Ser2‐oxyntomodulin,
interventions,
exercise,
time‐restricted
feeding,
adiponectin.
The
establishment
signaling
pathway
network
will
lead
advances
comprehension
cellular
mechanisms,
shedding
light
novel
treatments
promoting
aging‐associated
brain
health.
