International Immunopharmacology,
Год журнала:
2024,
Номер
145, С. 113742 - 113742
Опубликована: Дек. 5, 2024
Aortic
dissection
(AD)
is
a
life-threatening
aortopathy
with
no
specific
pharmacological
therapy.
Ubiquitination,
highly
orchestrated
enzymatic
cascade
involving
sequential
E1-E2-E3
interactions,
suggested
to
contribute
the
disease
pathogenesis.
However,
role
of
E1
enzymes
in
AD
progression
remains
unknown.
In
this
study,
we
analyzed
aortic
transcriptional
profiles
human
ascending
dataset
(GSE52093)
and
identified
ubiquitin-like
modifier-activating
enzyme
1
(UBA1)
as
significantly
up-regulated
AD.
This
finding
was
further
corroborated
by
immunohistochemistry
RT-qPCR
mouse
model
induced
β-aminopropionitrile
(BAPN).
Treatment
TAK-243,
UBA1
inhibitor,
prevented
BAPN-induced
formation
mice
attenuated
medial
degeneration,
evidenced
decreased
elastin
fragmentation
(evaluated
EVG
scoring),
reduced
vascular
smooth
muscle
cell
loss
(visualized
α-SMA
immunohistochemistry),
less
extracellular
matrix
degradation
(indicated
diminished
MMP2
MMP9
expression
RT-qPCR).
Furthermore,
TAK-243
treatment
lesional
macrophage
accumulation
activation,
demonstrated
CD68
analysis
pro-inflammatory
cytokine
expression.
vitro,
activation
observed
macrophages
(RAW264.7
cells)
treated
angiotensin
II
(AngII),
AngII-induced
at
least
partially
through
inhibition
IκBα
NF-κB
p65
phosphorylation.
conclusion,
demonstrate
that
may
facilitate
promoting
via
signaling
pathway.
These
findings
reveal
pathogenic
for
show
potential
UBA1-targeted
therapy
against
disease.
Cancers,
Год журнала:
2024,
Номер
16(8), С. 1563 - 1563
Опубликована: Апрель 19, 2024
Myelodysplastic
syndromes/neoplasms
(MDSs)
encompass
a
range
of
hematopoietic
malignancies,
commonly
affecting
elderly
individuals.
Molecular
alterations
in
the
stem
cell
compartment
drive
disease
pathogenesis.
Recent
advancements
genomic
profiling
have
provided
valuable
insights
into
biological
underpinnings
MDSs
and
expanded
therapeutic
options,
particularly
for
specific
molecularly
defined
subgroups.
This
review
highlights
diagnostic
principles,
classification
updates,
prognostic
stratification
systems,
novel
treatments,
which
could
inform
future
clinical
trials
enhance
management
adult
MDS
patients,
Journal of Investigative Medicine High Impact Case Reports,
Год журнала:
2025,
Номер
13
Опубликована: Апрель 1, 2025
VEXAS
syndrome,
a
myeloid-driven
autoinflammatory
disorder
associated
with
somatic
mutations
in
the
UBA1
gene,
was
first
described
2020
and
presents
significant
diagnostic
challenges
due
to
its
complex
clinical
features,
including
hematological
abnormalities
autoimmune
manifestations.
We
describe
case
involving
64-year-old
male
presenting
persistent
anemia,
weight
loss,
fatigue,
fever,
recurrent
inflammatory
symptoms.
Diagnostic
workup,
imaging,
serology,
bone
marrow
biopsy,
revealed
characteristic
findings,
myeloid
hyperplasia,
vacuolization
precursor
cells.
Genetic
testing
identified
gene
mutation,
solidifying
diagnosis
of
syndrome.
The
patient
responded
immunosuppressive
treatment
prednisone
ruxolitinib,
improvement
This
tells
us
importance
considering
syndrome
patients
refractory
systemic
inflammation
abnormalities,
particularly
older
males.
Early
recognition
genetic
are
crucial
for
guiding
decisions,
as
condition
is
progressive,
often
relapsing,
requires
multidisciplinary
management.
Journal of Clinical Medicine,
Год журнала:
2024,
Номер
13(22), С. 6970 - 6970
Опубликована: Ноя. 19, 2024
VEXAS
syndrome
is
a
recently
identified
autoinflammatory
disorder
resulting
from
somatic
mutations
in
the
UBA1
gene,
leading
to
complex
spectrum
of
severe
inflammatory
and
hematologic
manifestations.
The
absence
established
treatment
guidelines
variability
clinical
presentation
make
its
management
particularly
challenging.
Current
therapeutic
approaches
are
often
based
on
limited
evidence,
their
effectiveness
remains
inconsistent.
This
review
seeks
consolidate
existing
knowledge
strategies
for
syndrome,
offering
critical
evaluation
efficacy
addressing
gaps
current
literature.
As
recognition
grows,
there
an
urgent
need
explore
more
targeted,
effective
treatments
that
can
address
both
aspects
disease.
By
providing
comprehensive
analysis
landscape,
this
aims
guide
clinicians
researchers
toward
developing
effective,
long-term
life-threatening
condition.
Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Май 9, 2025
AbstractBackground:
Understanding
the
current
research
status
and
hotspots
of
VEXAS
(Vacuoles,
E1
enzyme,
X-linked,
Autoinflammatory,
Syndrome)
syndrome
provides
reference
guidance
for
diagnosis
treatment
syndrome.
Method:
Using
Web
Science
Core
Collection
(WOSCC)
literature
retrieval
platform,
we
filtered
related
to
conducted
a
visual
analysis
publication
volume,
authors,
publishing
institutions,
countries,
keywords
based
on
CiteSpace
6.3.R1.
Conclusion:
A
total
382
articles
were
obtained
through
results
filtering.
The
first
article
was
published
in
2020,
136
2024.
According
author
collaboration
network
analysis,
Beck
David
B
from
United
States
had
highest
number
publications,
with
27
articles.
Institution
country
revealed
that
APHP
National
Institutes
Health
while
count
(n=121).
top
ten
ranked
by
co-occurrence
mainly
revolve
around
definition,
mechanism,
clinical
manifestations
Keyword
cluster
indicates
main
features
are
inflammatory
hematological
manifestations,
its
mechanisms
characteristics
being
relatively
complex.
In
terms
treatment,
azacitidine
interferon-gamma
inhibitors,
IL-1
receptor
antagonists,
tumor
necrosis
factor
stem
cell
transplantation,
biological
agents
mentioned
succession.
primary
format
is
case
reports.
timeline
shows
sustained
intensity
onset
disease
present.
Burstness
focus
2020
definition
classification
From
2021
2022,
shifted
including
immunological
diseases
such
as
myelodysplastic
syndromes
(MDS),
chronic
monocytic
leukemia,
systemic
lupus
erythematosus,
polyarteritis
nodosa.
Conclusion:
has
gradually
attracted
attention
researchers,
an
overall
upward
trend
annual
although
publications
low.
Collaboration
between
authors
institutions
dispersed,
primarily
among
their
affiliated
lacking
cross-border
cooperation.
Currently,
lies
genetic
mutations,
immune
regulation,
multi-system
pathologic
presentations,
which
show
high
correlation
MDS
hematology.
lack
plans
standardized
protocols
may
be
short
duration
absence
large-scale
trials.
At
present,
analyses.
summary,
this
still
requires
more
practice,
mechanisms,
features,
strategies
should
explored
depth
lay
solid
foundation
effective
prevention
future.
Expert Review of Hematology,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 21, 2025
VEXAS
(vacuoles,
E1
enzyme,
X-linked,
autoinflammatory,
somatic)
syndrome
is
an
acquired
autoinflammatory
disorder
caused
by
somatic
mutations
in
the
UBA1
gene.
Predominantly
affecting
males
over
50,
disease
presents
with
systemic
inflammation,
hematologic
abnormalities,
and
features
of
clonal
hematopoiesis,
nearly
half
patients
developing
myelodysplastic
syndromes
(MDS).
The
interaction
between
inflammation
expansion
defines
progression,
emphasizing
need
for
a
comprehensive
understanding
its
pathogenesis
management.
This
review
discusses
clinical
spectrum,
genetic
landscape,
pathogenic
mechanisms
syndrome.
correlation
severity
explored,
alongside
role
hematopoiesis
inflammatory
pathways.
Current
treatments,
including
corticosteroids,
immunosuppressants,
JAK
inhibitors,
azacitidine,
are
evaluated
efficacy
limitations.
potential
allogeneic
hematopoietic
stem
cell
transplantation
(allo-HSCT)
as
curative
approach
also
addressed.
Literature
search
was
conducted
from
January
2020
to
present
using
PubMed
Scopus
databases
identify
relevant
studies.
reflects
complex
autoinflammation
hematopoiesis.
While
targeted
therapies
offer
symptomatic
control,
responses
remain
variable.
Future
strategies
should
focus
on
genotype-driven,
personalized
treatments
optimizing
allo-HSCT
protocols
improve
patient
outcomes
disease-modifying
potential.
Brain Sciences,
Год журнала:
2025,
Номер
15(6), С. 573 - 573
Опубликована: Май 26, 2025
VEXAS
syndrome
and
Alzheimer’s
disease
(AD),
though
distinct
in
clinical
manifestations,
share
overlapping
pathophysiological
mechanisms,
including
systemic
inflammation,
protein
misfolding,
vascular
dysfunction.
syndrome,
a
rare
autoinflammatory
disorder
characterized
by
somatic
UBA1
mutations,
hematologic
abnormalities,
presents
primarily
older
males.
Meanwhile,
AD,
the
leading
cause
of
dementia,
involves
progressive
neurodegeneration
driven
amyloid-beta
plaques,
tau
tangles,
chronic
neuroinflammation.
This
article
explores
potential
connections
between
two
conditions,
focusing
on
neurovascular
changes
cellular
stress.
Systemic
inflammation
observed
may
potentiate
neuroinflammatory
processes
as
circulating
proinflammatory
cytokines
have
capacity
to
cross
blood–brain
barrier
(BBB),
thereby
inducing
glial
activation
promoting
Additionally,
coexisting
dysfunctions
characteristic
both
conditions
synergistically
contribute
accelerated
cognitive
decline.
Both
involve
disruption
ubiquitin–proteasome
system,
with
mutations
being
specific
VEXAS.
Given
established
role
maintaining
neuronal
homeostasis,
investigating
molecular
mechanisms
provide
valuable
insights
into
their
pathophysiology.
The
review
underscores
need
for
further
research
elucidate
these
links
improve
therapeutic
strategies,
especially
individuals
affected
disorders.
