Philosophical Transactions of the Royal Society B Biological Sciences,
Journal Year:
2015,
Volume and Issue:
370(1667), P. 20140120 - 20140120
Published: March 17, 2015
Over
the
past
3
billion
years,
an
endogenous
circadian
rhythmicity
has
developed
in
almost
all
life
forms
which
daily
oscillations
physiology
occur.
This
allows
for
anticipation
of
sunrise
and
sunset.
physiological
is
kept
at
precisely
24
h
by
cycle
sunlight
dark.
However,
since
introduction
electric
lighting,
there
been
inadequate
light
during
day
inside
buildings
a
robust
resetting
human
rhythmicity,
too
much
night
true
dark
to
be
detected;
this
results
disruption
alters
sleep/wake
cycle,
core
body
temperature,
hormone
regulation
release,
patterns
gene
expression
throughout
body.
The
question
extent
compromises
health,
can
account
portion
modern
pandemics
breast
prostate
cancers,
obesity,
diabetes
depression.
As
societies
modernize
(i.e.
electrify)
these
conditions
increase
prevalence.
There
are
number
promising
leads
on
putative
mechanisms,
epidemiological
findings
supporting
aetiologic
role
lighting
disease
causation.
These
include
melatonin
suppression,
expression,
connection
metabolism
part
affected
haem
iron
intake
distribution.
Cells,
Journal Year:
2019,
Volume and Issue:
8(11), P. 1419 - 1419
Published: Nov. 11, 2019
Liver
fibrosis
is
an
advanced
liver
disease
condition,
which
could
progress
to
cirrhosis
and
hepatocellular
carcinoma.
To
date,
there
no
direct
approved
antifibrotic
therapy,
current
treatment
mainly
the
removal
of
causative
factor.
Transforming
growth
factor
(TGF)-β
a
master
profibrogenic
cytokine
promising
target
treat
fibrosis.
However,
TGF-β
has
broad
biological
functions
its
inhibition
induces
non-desirable
side
effects,
override
therapeutic
benefits.
Therefore,
understanding
pleiotropic
effects
upstream
downstream
regulatory
mechanisms
will
help
design
better
based
therapeutics.
Here,
we
summarize
recent
discoveries
milestones
on
signaling
pathway
related
hepatic
stellate
cell
(HSC)
activation,
emphasizing
research
last
five
years.
This
comprises
impact
fibrogenesis
processes,
such
as
senescence,
metabolism,
reactive
oxygen
species
generation,
epigenetics,
circadian
rhythm,
epithelial
mesenchymal
transition,
endothelial-mesenchymal
transition.
We
also
describe
influence
microenvironment
response
HSC
TGF-β.
Finally,
discuss
new
approaches
pathway,
name
clinical
trials,
explain
promises
drawbacks
that
deserve
be
adequately
addressed.
Protein Science,
Journal Year:
2018,
Volume and Issue:
27(11), P. 1876 - 1892
Published: Aug. 15, 2018
Abstract
Nuclear
receptors
(NRs)
are
a
family
of
transcription
factors
that
regulate
numerous
physiological
processes
such
as
metabolism,
reproduction,
inflammation,
well
the
circadian
rhythm.
NRs
sense
changes
in
lipid
metabolite
levels
to
drive
differential
gene
expression,
producing
distinct
physiologic
effects.
This
is
an
allosteric
process
whereby
binding
cognate
ligand
and
specific
DNA
sequences
drives
recruitment
diverse
transcriptional
co‐regulators
at
chromatin
ultimately
transactivation
or
transrepression
target
genes.
Dysregulation
NR
signaling
leads
various
malignances,
metabolic
disorders,
inflammatory
disease.
Given
their
important
role
physiology
ability
respond
small
lipophilic
ligands,
have
emerged
valuable
therapeutic
targets.
Here,
we
summarize
discuss
recent
progress
on
understanding
complex
mechanism
action
NRs,
primarily
from
structural
perspective.
Finally,
suggest
future
studies
improve
our
better
design
drugs
by
integrating
multiple
biophysical
approaches.
Journal of Medicinal Chemistry,
Journal Year:
2020,
Volume and Issue:
63(23), P. 14243 - 14275
Published: Sept. 1, 2020
Sulfoximines
have
been
largely
disregarded
in
medicinal
chemistry
for
a
long
time.
However,
recently,
they
risen
to
the
apparent
level
of
stardom
on
drug
discovery
scene.
Considering
outstanding
properties
sulfoximines,
this
versatile
functional
group
has
advanced
implementation
several
programs.
Currently,
fashionable
can
be
found
various
hit-to-lead
and
lead
optimization
studies
early
stages
compounds
currently
clinical
trials.
Herein,
we
review
recent
developments
demonstrate
scope
limitations
interesting
discovery.
