Journal of Molecular Biology,
Journal Year:
2025,
Volume and Issue:
unknown, P. 168937 - 168937
Published: Jan. 1, 2025
The
phosphoinositide
family
of
membrane
lipids
play
diverse
and
critical
roles
in
eukaryotic
molecular
biology.
Much
this
biological
activity
derives
from
interactions
with
integral
peripheral
proteins,
leading
to
modulation
protein
structure,
function,
cellular
distribution.
Since
the
discovery
phosphoinositides
1940s,
combined
biology,
biophysical,
structural
approaches
have
made
enormous
progress
untangling
vast
network
interactions.
More
recently,
silico
such
as
dynamics
simulations
proven
be
an
asset
prospectively
identifying,
characterising,
explaining
basis
these
interactions,
best
cases
providing
atomic
level
testable
hypotheses
on
how
control
function
a
given
protein.
This
review
details
number
recent
seminal
discoveries
enabled
by
advanced
biomolecular
simulation,
its
integration
biology
approaches.
results
simulation
studies
agree
well
experimental
work,
notable
arrived
at
key
conclusion
several
years
advance
structures.
Condensed
title:Simulations
proteins
SUMMARY:
Hedger
Yen
developments
proteins.
Pharmacological Research,
Journal Year:
2025,
Volume and Issue:
212, P. 107574 - 107574
Published: Jan. 2, 2025
G
protein-coupled
receptors
(GPCRs)
represent
the
largest
family
of
membrane
and
are
highly
effective
targets
for
therapeutic
drugs.
GPCRs
couple
different
downstream
effectors,
including
proteins
(such
as
Gi/o,
Gs,
G12,
Gq)
β-arrestins
β-arrestin
1
2)
to
mediate
diverse
cellular
physiological
responses.
Biased
signaling
allows
specific
activation
certain
pathways
from
full
range
receptors'
capabilities.
Targeting
more
variable
allosteric
sites,
which
spatially
conserved
orthosteric
represents
a
novel
approach
in
biased
GPCR
drug
discovery,
leading
innovative
strategies
targeting
GPCRs.
Notably,
emergence
cryptic
sites
on
has
expanded
repertoire
available
improved
receptor
subtype
selectivity.
Here,
we
conduct
summary
recent
progress
structural
determination
elucidate
mechanisms
induced
by
modulators.
Additionally,
discuss
means
identify
design
modulators
based
through
structure-based
design,
is
an
advanced
pharmacotherapeutic
treating
GPCR-associated
diseases.
Cell Research,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 29, 2025
Abstract
Sleep
deficiency
is
associated
with
obesity,
but
the
mechanisms
underlying
this
connection
remain
unclear.
Here,
we
identify
a
sleep-inducible
hypothalamic
protein
hormone
in
humans
and
mice
that
suppresses
obesity.
This
cleaved
from
reticulocalbin-2
(RCN2),
name
it
Raptin.
Raptin
release
timed
by
circuit
vasopressin-expressing
neurons
suprachiasmatic
nucleus
to
RCN2-positive
paraventricular
nucleus.
levels
peak
during
sleep,
which
blunted
sleep
deficiency.
binds
glutamate
metabotropic
receptor
3
(GRM3)
of
hypothalamus
stomach
inhibit
appetite
gastric
emptying,
respectively.
Raptin-GRM3
signaling
mediates
anorexigenic
effects
via
PI3K-AKT
signaling.
Of
note,
verify
connections
between
deficiencies
sleeping
state,
impaired
release,
obesity
patients
Moreover,
carrying
an
RCN2
nonsense
variant
present
night
eating
syndrome
These
data
define
unique
food
intake
prevents
Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: Dec. 5, 2024
Abstract
Neutrophils,
the
most
abundant
type
of
granulocyte,
are
widely
recognized
as
one
pivotal
contributors
to
acute
inflammatory
response.
Initially,
neutrophils
were
considered
mobile
infantry
innate
immune
system,
tasked
with
immediate
response
invading
pathogens.
However,
recent
studies
have
demonstrated
that
versatile
cells,
capable
regulating
various
biological
processes
and
impacting
both
human
health
disease.
Cytokines
other
active
mediators
regulate
functional
activity
by
activating
multiple
receptors
on
these
thereby
initiating
downstream
signal
transduction
pathways.
Dysfunctions
in
disruptions
neutrophil
homeostasis
been
implicated
pathogenesis
numerous
diseases,
including
cancer
disorders,
often
due
aberrant
intracellular
signaling.
This
review
provides
a
comprehensive
synthesis
functions,
integrating
advancements
this
field.
Moreover,
it
examines
roles
signaling
pathways
involved
regulation
activity.
The
pathophysiology
diseases
emerging
therapeutic
approaches
targeting
them
also
elaborated.
addresses
current
limitations
within
field
research,
highlighting
critical
gaps
knowledge
warrant
further
investigation.
In
summary,
seeks
establish
multidimensional
model
regulation,
providing
new
perspectives
for
potential
clinical
applications
research.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(2), P. 703 - 703
Published: Jan. 15, 2025
The
approaches
to
correct
thyroid
deficiency
include
replacement
therapy
with
hormones
(THs),
but
such
causes
a
number
of
side
effects.
A
possible
alternative
is
thyroid-stimulating
hormone
(TSH)
receptor
activators,
including
allosteric
agonists.
aim
this
work
was
study
the
effect
ethyl-2-(4-(4-(5-amino-6-(tert-butylcarbamoyl)-2-(methylthio)thieno[2,3-d]pyrimidin-4-yl)phenyl)-1H-1,2,3-triazol-1-yl)
acetate
(TPY3m),
TSH
agonist
developed
by
us,
on
basal
and
thyroliberin
(TRH)-stimulated
TH
levels
hypothalamic-pituitary-thyroid
(HPT)
axis
in
male
rats
high-fat
diet/low-dose
streptozotocin-induced
type
2
diabetes
mellitus
(T2DM).
Single
three-day
administration
TPY3m
(i.p.,
20
mg/kg)
studied,
HPT
compared
that
levothyroxine.
increased
when
administered
both
healthy
diabetic
rats,
normalizing
thyroxine
triiodothyronine
T2DM
and,
unlike
levothyroxine,
without
negatively
affecting
or
expression
hypothalamic
pituitary
genes
responsible
for
production.
pretreatment
preserved
stimulatory
effects
TRH
gene
expression.
This
indicates
absence
competition
between
endogenous
activation
supported
our
vitro
results
TPY3m-
TSH-stimulated
adenylate
cyclase
activity
rat
membranes.
Morphological
analysis
glands
after
shows
an
increase
its
functional
destructive
changes.
To
summarize,
TPY3m,
partial
receptor,
created
as
prototype
drugs
insufficiency
T2DM.
Microbial Biotechnology,
Journal Year:
2025,
Volume and Issue:
18(1)
Published: Jan. 1, 2025
ABSTRACT
Advancing
microbiome–gut–brain
axis
science
requires
systematic,
rational
and
translational
approaches
to
bridge
the
critical
knowledge
gaps
currently
preventing
full
exploitation
of
gut
microbiome
as
a
tractable
therapeutic
target
for
gastrointestinal,
mental
brain
health.
Current
research
is
still
marked
by
many
open
questions
that
undermine
widespread
application
humans.
For
example,
lack
mechanistic
understanding
probiotic
effects
means
it
remains
unclear
why
even
apparently
closely
related
strains
exhibit
different
in
vivo.
live
microbial
psychobiotics,
consensus
on
their
adjunct
treatments
conventional
neuromodulators,
use
unmedicated
populations
or
at‐risk
cohorts
with
sub‐clinical
symptomatology
warranted.
This
missing
information
both
sides
equation
when
treating
central
nervous
system
(CNS)
conditions
makes
psychobiotic
challenging,
especially
compared
other
pharmaceutical
functional
food
approaches.
Expediting
transition
from
positive
preclinical
data
proven
benefits
humans
includes
interpreting
promises
pitfalls
animal
behavioural
assays,
well
navigating
mechanism‐informed
decision
making
select
right
microbe(s)
job.
In
this
review,
we
consider
how
these
decisions
can
be
supported
light
accrued
range
clinical
studies
across
healthy,
pathological
study
populations,
where
specific
have
been
evaluated
context
gastrointestinal
physiology,
function
behaviour.
Examples
successful,
partial
unsuccessful
translation
bench
bedside
are
considered.
We
also
discuss
developments
silico
analyses
enhanced
our
moved
towards
pinpointing
host–microbe
interactions
most
important
optimal
gut–brain
function.
Combining
assays
vitro
ex
vivo
domains
incorporating
model
organisms
prime
discovery
pipelines
promising
rationally
selected
candidates.
