Acta Pharmaceutica Sinica B,
Journal Year:
2024,
Volume and Issue:
15(1), P. 278 - 295
Published: Nov. 27, 2024
Intestinal
fibrosis
is
a
significant
clinical
challenge
in
inflammatory
bowel
diseases,
but
no
effective
anti-fibrotic
therapy
currently
available.
Glucagon
receptor
(GCGR)
and
glucagon-like
peptide
1
(GLP1R)
are
both
hormone
receptors
involved
energy
metabolism
of
epithelial
cells.
However,
their
role
intestinal
the
underlying
mechanisms
remain
largely
unexplored.
Herein
GCGR
GLP1R
were
found
to
be
reduced
stenotic
ileum
patients
with
Crohn's
disease
as
well
fibrotic
colon
mice
chronic
colitis.
The
downregulation
led
accumulation
metabolic
byproduct
lactate,
resulting
histone
H3K9
lactylation
exacerbated
through
epithelial-to-mesenchymal
transition
(EMT).
Dual
activating
by
1907B
cells
ameliorated
vivo.
We
uncovered
GCGR/GLP1R
regulating
EMT
via
lactylation.
Simultaneously
novel
dual
agonist
holds
promise
treatment
strategy
for
alleviating
fibrosis.
Journal of Advanced Research,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 1, 2025
The
modification
of
endothelial
cells
(ECs)
biological
function
under
pathogenic
conditions
leads
to
the
expression
mesenchymal
stromal
(MSCs)
markers,
defined
as
endothelial-to-mesenchymal
transition
(EndMT).
Invisible
in
onset
and
slow
progression,
atherosclerosis
(AS)
is
a
potential
contributor
various
atherosclerotic
cardiovascular
diseases
(ASCVD).
By
triggering
AS,
EndMT,
"initiator"
induces
progression
ASCVD
such
coronary
heart
disease
(CHD)
ischemic
cerebrovascular
(ICD),
with
serious
clinical
complications
myocardial
infarction
(MI)
stroke.
In-depth
research
pathomechanisms
EndMT
identification
targeted
therapeutic
strategies
hold
considerable
value
for
prevention
treatment
ASCVD-associated
delayed
EndMT.
Although
previous
studies
have
progressively
unraveled
complexity
its
pathogenicity
triggered
by
alterations
vascular
microenvironmental
factors,
systematic
descriptions
most
recent
roles
strategies,
their
future
directions
are
scarce.
Theranostics,
Journal Year:
2025,
Volume and Issue:
15(5), P. 1787 - 1821
Published: Jan. 2, 2025
Lactate
is
an
indispensable
substance
in
various
cellular
physiological
functions
and
plays
regulatory
roles
different
aspects
of
energy
metabolism
signal
transduction.
Lactylation
(Kla),
a
key
pathway
through
which
lactate
exerts
its
functions,
has
been
identified
as
novel
posttranslational
modification
(PTM).
Research
indicates
that
Kla
essential
balancing
mechanism
variety
organisms
involved
many
biological
processes
pathways.
closely
related
to
disease
development
represents
potential
important
new
drug
target.
In
line
with
existing
reports,
we
searched
for
newly
discovered
sites
on
histone
nonhistone
proteins;
reviewed
the
mechanisms
(particularly
focusing
enzymes
directly
reversible
regulation
Kla,
including
"writers"
(modifying
enzymes),
"readers"
(modification-binding
"erasers"
(demodifying
enzymes);
summarized
crosstalk
between
PTMs
help
researchers
better
understand
widespread
distribution
diverse
functions.
Furthermore,
considering
"double-edged
sword"
role
both
pathological
contexts,
this
review
highlights
"beneficial"
states
(energy
metabolism,
inflammatory
responses,
cell
fate
determination,
development,
etc.)
"detrimental"
pathogenic
or
inducive
effects
processes,
particularly
malignant
tumors
complex
nontumor
diseases.
We
also
clarify
molecular
health
disease,
discuss
feasibility
therapeutic
Finally,
describe
detection
technologies
their
applications
diagnosis
clinical
settings,
aiming
provide
insights
treatment
diseases
accelerate
translation
from
laboratory
research
practice.
Frontiers in Cell and Developmental Biology,
Journal Year:
2025,
Volume and Issue:
13
Published: March 28, 2025
Lactate,
as
a
metabolic
product
or
energy
substrate,
participates
in
various
neurological
processes
within
the
physiological
and
pathological
frameworks
of
central
nervous
system
(CNS).
The
groundbreaking
application
multi-omics
integration
technologies
has
unveiled
novel
role
for
lactate:
lactylation,
unique
post-translational
modification
(PTM)
that
covalently
attaches
lactate
groups
to
lysine
residues
on
proteins.
This
process
precisely
regulates
protein
function
gene
expression,
profoundly
influencing
progression
diseases.
lactylation
is
meticulously
regulated
by
variety
key
enzymes
pathways,
forming
dynamic
intricate
network.
In
this
review,
we
summarize
involved
specifically
"Writers,"
"Erasers,"
"Readers."
Furthermore,
systematically
categorize
observed
cell
types
CNS
investigate
its
multifaceted
roles
processes,
including
neurodegenerative
diseases,
brain
tumors,
injuries.
By
consolidating
latest
research
findings
field,
our
review
aims
highlight
significance
these
discoveries
future
explore
their
potential
translational
applications.
Cell Death Discovery,
Journal Year:
2025,
Volume and Issue:
11(1)
Published: April 30, 2025
Lactate,
the
end
product
of
glycolysis,
plays
a
crucial
role
in
cellular
signaling
and
metabolism.
The
discovery
lactylation,
novel
post-translational
modification,
has
uncovered
lactate
regulating
diseases,
especially
brain.
Lactylation
connects
genetic
encoding
with
protein
function,
thereby
influencing
key
biological
processes.
Increasing
evidence
supports
lactate-mediated
lactylation
as
critical
modulator
neurological
disorders.
This
review
offers
an
overview
metabolism
highlighting
recent
advances
understanding
regulatory
enzymes
their
central
nervous
system.
We
investigate
impact
on
brain
dysfunctions,
including
neurodegenerative
cerebrovascular
disorders,
neuroinflammation,
tumors,
psychiatric
conditions.
Moreover,
we
highlight
therapeutic
potential
targeting
treating
disorders
outline
research
gaps
future
directions
needed
to
advance
this
promising
field.
Cells,
Journal Year:
2025,
Volume and Issue:
14(5), P. 378 - 378
Published: March 5, 2025
Endothelial
dysfunction
is
the
main
initiating
factor
in
atherosclerosis.
Through
mechanotransduction,
shear
stress
regulates
endothelial
cell
function
both
homeostatic
and
diseased
states.
Accumulating
evidence
reveals
that
epigenetic
changes
play
critical
roles
etiology
of
cardiovascular
diseases,
including
The
metabolic
regulation
epigenetics
has
emerged
as
an
important
control
gene
expression
states,
but
to
best
our
knowledge,
this
connection
remains
largely
unexplored
In
review,
we
(1)
summarize
how
(or
flow)
(dys)function;
(2)
explore
alterations
occur
endothelium
response
disturbed
flow;
(3)
review
metabolism
under
different
conditions;
(4)
suggest
mechanisms
which
may
link
altered
epigenome
by
modulations
metabolite
availability.
We
believe
plays
role
reprogramming
could
pave
way
for
novel
metabolism-based
therapeutic
strategies.
