MedComm,
Journal Year:
2023,
Volume and Issue:
4(3)
Published: June 1, 2023
Type
2
diabetes
mellitus
(T2DM)
represents
one
of
the
fastest
growing
epidemic
metabolic
disorders
worldwide
and
is
a
strong
contributor
for
broad
range
comorbidities,
including
vascular,
visual,
neurological,
kidney,
liver
diseases.
Moreover,
recent
data
suggest
mutual
interplay
between
T2DM
Corona
Virus
Disease
2019
(COVID-19).
characterized
by
insulin
resistance
(IR)
pancreatic
β
cell
dysfunction.
Pioneering
discoveries
throughout
past
few
decades
have
established
notable
links
signaling
pathways
pathogenesis
therapy.
Importantly,
number
substantially
control
advancement
core
pathological
changes
in
T2DM,
IR
dysfunction,
as
well
additional
pathogenic
disturbances.
Accordingly,
an
improved
understanding
these
sheds
light
on
tractable
targets
strategies
developing
repurposing
critical
therapies
to
treat
its
complications.
In
this
review,
we
provide
brief
overview
history
pathways,
offer
systematic
update
role
mechanism
key
underlying
onset,
development,
progression
T2DM.
content,
also
summarize
current
therapeutic
drugs/agents
associated
with
treatment
complications,
discuss
some
implications
directions
future
field.
Journal of Translational Medicine,
Journal Year:
2023,
Volume and Issue:
21(1)
Published: Dec. 8, 2023
AMP-activated
protein
kinase
(AMPK)
is
a
ubiquitous
sensor
of
energy
and
nutritional
status
in
eukaryotic
cells.
It
plays
key
role
regulating
cellular
homeostasis
multiple
aspects
cell
metabolism.
During
macrophage
polarisation,
AMPK
not
only
guides
the
metabolic
programming
macrophages,
but
also
counter-regulates
inflammatory
function
macrophages
promotes
their
polarisation
toward
anti-inflammatory
phenotype.
located
at
intersection
metabolism
inflammation.
The
characteristics
are
closely
related
to
immune-related
diseases,
infectious
cancer
progression
immunotherapy.
This
review
discusses
structure
its
metabolism,
macrophages.
In
addition,
it
summarises
important
pathway
activators
development
macrophage-related
diseases.
Cell Research,
Journal Year:
2024,
Volume and Issue:
34(3), P. 214 - 231
Published: Feb. 8, 2024
Abstract
Flickering
light
stimulation
has
emerged
as
a
promising
non-invasive
neuromodulation
strategy
to
alleviate
neuropsychiatric
disorders.
However,
the
lack
of
neurochemical
underpinning
hampered
its
therapeutic
development.
Here,
we
demonstrate
that
flickering
triggered
an
immediate
and
sustained
increase
(up
3
h
after
flickering)
in
extracellular
adenosine
levels
primary
visual
cortex
(V1)
other
brain
regions,
function
frequency
intensity,
with
maximal
effects
observed
at
40
Hz
4000
lux.
We
uncovered
cortical
(glutamatergic
GABAergic)
neurons,
rather
than
astrocytes,
cellular
source,
intracellular
generation
from
AMPK-associated
energy
metabolism
pathways
(but
not
SAM-transmethylation
or
salvage
purine
pathways),
efflux
mediated
by
equilibrative
nucleoside
transporter-2
(ENT2)
molecular
pathway
responsible
for
generation.
Importantly,
20
80
Hz)
30
min
enhanced
non-rapid
eye
movement
(non-REM)
REM
sleep
2–3
mice.
This
somnogenic
effect
was
abolished
ablation
V1
superior
colliculus)
neurons
genetic
deletion
gene
encoding
ENT2
ENT1),
but
recaptured
chemogenetic
inhibition
focal
infusion
into
dose-dependent
manner.
Lastly,
also
promoted
children
insomnia
decreasing
onset
latency,
increasing
total
time,
reducing
waking
onset.
Collectively,
our
findings
establish
ENT2-mediated
signaling
basis
flickering-induced
unravel
novel
treatment
insomnia,
condition
affects
20%
world
population.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: March 8, 2024
Abstract
Neuronal
mitochondria
play
important
roles
beyond
ATP
generation,
including
Ca
2+
uptake,
and
therefore
have
instructive
in
synaptic
function
neuronal
response
properties.
Mitochondrial
morphology
differs
significantly
between
the
axon
dendrites
of
a
given
subtype,
but
CA1
pyramidal
neurons
(PNs)
hippocampus,
within
dendritic
arbor
also
display
remarkable
degree
subcellular,
layer-specific
compartmentalization.
In
these
neurons,
ranges
from
highly
fused
elongated
apical
tuft,
to
more
fragmented
oblique
basal
compartments,
thus
occupy
smaller
fraction
volume
than
tuft.
However,
molecular
mechanisms
underlying
this
striking
subcellular
compartmentalization
are
unknown,
precluding
assessment
its
impact
on
function.
Here,
we
demonstrate
that
compartment-specific
requires
activity-dependent,
Camkk2-dependent
activation
AMPK
ability
phosphorylate
two
direct
effectors:
pro-fission
Drp1
receptor
Mff
recently
identified
anti-fusion,
Opa1-inhibiting
protein,
Mtfr1l.
Our
study
uncovers
signaling
pathway
mitochondrial
vivo
through
spatially
precise
activity-dependent
regulation
fission/fusion
balance.
Molecular Cell,
Journal Year:
2024,
Volume and Issue:
84(6), P. 1120 - 1138.e8
Published: Feb. 19, 2024
UFMylation
is
an
emerging
ubiquitin-like
post-translational
modification
that
regulates
various
biological
processes.
Dysregulation
of
the
pathway
leads
to
human
diseases,
including
cancers.
However,
physiological
role
in
T
cells
remains
unclear.
Here,
we
report
mice
with
conditional
knockout
(cKO)
Ufl1,
a
E3
ligase,
exhibit
effective
tumor
control.
Single-cell
RNA
sequencing
analysis
shows
tumor-infiltrating
cytotoxic
CD8+
are
increased
Ufl1
cKO
mice.
Mechanistically,
UFL1
promotes
PD-1
antagonize
ubiquitination
and
degradation.
Furthermore,
AMPK
phosphorylates
at
Thr536,
disrupting
trigger
its
Of
note,
ablation
reduces
UFMylation,
subsequently
destabilizing
enhancing
cell
activation.
Thus,
bearing
tumors
have
better
response
anti-CTLA-4
immunotherapy.
Collectively,
our
findings
uncover
crucial
highlight
as
potential
target
for
cancer
treatment.
