Russian Journal of Allergy,
Journal Year:
2024,
Volume and Issue:
21(2), P. 265 - 282
Published: May 20, 2024
Chronic
spontaneous
urticaria
is
a
fairly
common
disease
with
an
unpredictable
course,
burdensome
symptoms
and
significant
negative
impact
on
patients`
quality
of
life.
Despite
the
established
stepwise
approach
to
treatment
antihistamines
in
standard
increased
dosages,
anti-IgE
therapy,
there
remains
portion
patients
unsatisfactory
control
symptoms,
need
develop
drugs
that
target
new
therapeutic
targets.
Mast
cells,
basophils
B
cells
are
key
involved
pathogenesis
urticaria;
activation,
differentiation,
proliferation,
cytokine
secretion
degranulation
all
three
types
regulated
via
Bruton's
tyrosine
kinase
signalling
pathway
through
FcεRI
BCR
receptors
respectively.
Inhibition
being
developed
as
strategy
for
chronic
urticaria.
Here
we
present
overview
current
understanding
urticarial`s
pathogenesis,
role
kinase,
history
medical
use
inhibitors,
well
clinical
data
inhibitors
who
have
not
achieved
adequate
antihistamines.
Journal of Hematology & Oncology,
Journal Year:
2025,
Volume and Issue:
18(1)
Published: Jan. 13, 2025
The
tumor
microenvironment
(TME)
is
integral
to
cancer
progression,
impacting
metastasis
and
treatment
response.
It
consists
of
diverse
cell
types,
extracellular
matrix
components,
signaling
molecules
that
interact
promote
growth
therapeutic
resistance.
Elucidating
the
intricate
interactions
between
cells
TME
crucial
in
understanding
progression
challenges.
A
critical
process
induced
by
epithelial-mesenchymal
transition
(EMT),
wherein
epithelial
acquire
mesenchymal
traits,
which
enhance
their
motility
invasiveness
progression.
By
targeting
various
components
TME,
novel
investigational
strategies
aim
disrupt
TME's
contribution
EMT,
thereby
improving
efficacy,
addressing
resistance,
offering
a
nuanced
approach
therapy.
This
review
scrutinizes
key
players
emphasizing
avenues
therapeutically
components.
Moreover,
article
discusses
implications
for
resistance
mechanisms
highlights
current
toward
modulation
along
with
potential
caveats.
Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
67(2), P. 864 - 884
Published: Jan. 10, 2024
The
DNA-encoded
library
(DEL)
discovery
platform
has
emerged
as
a
powerful
technology
for
hit
identification
in
recent
years.
It
become
one
of
the
major
parallel
workstreams
small
molecule
drug
along
with
other
strategies
such
HTS
and
data
mining.
For
many
researchers
working
DEL
field,
it
increasingly
evident
that
hits
leads
discovered
via
screening
bind
to
target
proteins
unique
unprecedented
binding
modes.
This
Perspective
is
our
attempt
analyze
reports
purpose
providing
rigorous
useful
account
modes
observed
DEL-derived
ligands
focus
on
mode
novelty.
Brain Pathology,
Journal Year:
2024,
Volume and Issue:
34(5)
Published: Jan. 22, 2024
Abstract
Activation
of
Bruton's
tyrosine
kinase
(BTK)
has
been
shown
to
play
a
crucial
role
in
the
proinflammatory
response
B
cells
and
myeloid
upon
engagement
with
cell,
Fc,
Toll‐like
receptor,
distinct
chemokine
receptors.
Previous
reports
suggest
BTK
actively
contributes
pathogenesis
multiple
sclerosis
(MS).
The
inhibitor
Evobrutinib
reduce
numbers
gadolinium‐enhancing
lesions
relapses
relapsing–remitting
MS
patients.
In
vitro,
inhibition
resulted
reduced
phagocytic
activity
modulated
BTK‐dependent
inflammatory
signaling
microglia
macrophages.
Here,
we
investigated
protein
expression
CD68
as
well
iron
accumulation
postmortem
control
(
n
=
10)
23)
brain
tissue,
focusing
on
cases
encompassed
active,
chronic
inactive
lesions.
+
positively
correlated
across
all
regions
interests
and,
along
CD68,
revealed
highest
center
active
at
rim
We
then
studied
effect
human
immortalized
microglia‐like
HMC3
cell
line
vitro.
particular,
loaded
iron‐dextran
subsequently
administered
Evobrutinib.
Iron
treatment
alone
induced
phenotype
increased
importers
intracellular
storage
ferritin
light
chain
(FTL).
iron‐laden
dampened
microglia‐related
genes
iron‐importers,
whereas
iron‐exporter
ferroportin
was
upregulated.
Our
data
that
not
only
dampens
but
also
reduces
import
activated
macrophages
possible
implications
microglial
MS.
Journal of Allergy and Clinical Immunology,
Journal Year:
2023,
Volume and Issue:
153(5), P. 1229 - 1240
Published: Dec. 21, 2023
Chronic
spontaneous
urticaria
(CSU)
is
an
inflammatory
skin
disorder
that
manifests
with
itchy
wheals,
angioedema,
or
both
for
>6
weeks.
Mast
cells
(MCs)
and
basophils
are
the
key
pathogenic
drivers
of
CSU;
their
activation
results
in
histamine
cytokine
release
subsequent
dermal
inflammation.
Two
overlapping
mechanisms
MC
basophil
have
been
proposed
CSU:
type
I
autoimmunity,
also
called
autoallergy,
mediated
via
IgE
against
various
autoallergens,
IIb
predominantly
IgG
directed
receptor
FcεRI
FcεRI-bound
IgE.
Both
involve
cross-linking
downstream
signaling
pathways
may
co-occur
same
patient.
In
addition,
B-cell
(BCR)
has
postulated
to
play
a
role
CSU
by
generating
autoreactive
B
autoantibody
production.
A
cornerstone
BCR
Bruton's
tyrosine
kinase
(BTK),
making
BTK
inhibition
clear
therapeutic
target
CSU.
The
potential
application
early-generation
inhibitors,
including
ibrutinib,
allergic
autoimmune
diseases
limited
due
unfavorable
benefit–risk
profile.
However,
novel
inhibitors
improved
selectivity
safety
profiles
developed
under
clinical
investigation
diseases,
Phase
2
trials,
remibrutinib
fenebrutinib
demonstrated
rapid
sustained
improvements
disease
activity.
With
3
studies
ongoing,
it
hoped
will
present
effective,
well-tolerated
option
patients
antihistamine-refractory
CSU,
phenotype
presents
considerable
challenge.
Frontiers in Oncology,
Journal Year:
2024,
Volume and Issue:
14
Published: March 20, 2024
Hematopoiesis
is
a
tightly
regulated
process
that
produces
all
adult
blood
cells
and
immune
from
multipotent
hematopoietic
stem
(HSCs).
HSCs
usually
remain
quiescent,
in
the
presence
of
external
stimuli
like
infection
or
inflammation,
they
undergo
division
differentiation
as
compensatory
mechanism.
Normal
hematopoiesis
impacted
by
systemic
which
causes
to
transition
quiescence
emergency
myelopoiesis.
At
molecular
level,
inflammatory
cytokine
signaling
molecules
such
tumor
necrosis
factor
(TNF),
interferons,
interleukins,
toll-like
receptors
can
cause
multiply
directly.
These
cytokines
actively
encourage
HSC
activation,
proliferation,
during
results
generation
activation
required
combat
acute
injury.
The
bone
marrow
niche
provides
numerous
soluble
stromal
cell
signals,
are
essential
for
maintaining
normal
homeostasis
output
cells.
Inflammatory
signals
also
impact
this
microenvironment
called
regulate
inflammatory-induced
hematopoiesis.
Continuous
pro-inflammatory
chemokine
have
detrimental
effects
on
system,
lead
cancer
development,
depletion,
failure.
Reactive
oxygen
species
(ROS),
damage
DNA
ultimately
transformation
into
cancerous
cells,
produced
due
chronic
inflammation.
biological
elements
produce
clonal
growth
development
leukemic
(LSCs)
hematological
malignancies.
processes
underlying
how
inflammation
affects
malignancies
still
not
fully
understood.
In
review,
we
emphasize
hematopoiesis,
part
it
plays
progression
malignancies,
potential
therapeutic
applications
targeting
these
pathways
therapy
Life,
Journal Year:
2023,
Volume and Issue:
13(7), P. 1496 - 1496
Published: July 1, 2023
Systemic
lupus
erythematosus
(SLE),
the
prototype
of
systemic
autoimmune
diseases
is
characterized
by
extreme
heterogeneity
with
a
variable
clinical
course.
Renal
involvement
may
be
observed
and
affects
outcome.
Hydroxychloroquine
should
administered
to
every
patient
irrespective
organ
involvement.
Conventional
immunosuppressive
therapy
includes
corticosteroids,
methotrexate,
cyclophosphamide,
mycophenolate
mofetil,
azathioprine,
cyclosporine
tacrolimus.
However,
despite
conventional
treatment,
flares
occur
broad
immunosuppression
accompanied
multiple
side
effects.
Flare
occurrence,
target
involvement,
effects
increased
knowledge
pathogenetic
mechanisms
involved
in
SLE
pathogenesis
as
well
availability
biologic
agents
has
led
application
management.
Biologic
targeting
various
paths
have
been
applied.
B
cell
used
successfully.
Belimumab,
agent,
approved
for
treatment
SLE.
Rituximab,
an
anti-CD20
agent
also
Anifrolumab,
interferon
I
receptor-targeting
beneficial
on
In
conclusion,
applied
further
evaluated
aim
good
response
significant
improvement
quality
life.
Annals of the Rheumatic Diseases,
Journal Year:
2023,
Volume and Issue:
83(3), P. 360 - 371
Published: Nov. 6, 2023
Objectives
To
evaluate
the
safety
and
efficacy
of
remibrutinib
in
patients
with
moderate-to-severe
Sjögren’s
syndrome
(SjS)
a
phase
2
randomised,
double-blind
trial
(
NCT04035668
;
LOUiSSE
(LOU064
Syndrome)
study).
Methods
Eligible
fulfilling
2016
American
College
Rheumatology/European
League
Against
Rheumatism
(EULAR)
criteria
for
SjS,
positive
anti-Ro/Sjögren’s
syndrome-related
antigen
A
antibodies,
disease
activity
(EULAR
Syndrome
Disease
Activity
Index
(ESSDAI)
(based
on
weighted
score)
≥
5,
EULAR
Patient
Reported
(ESSPRI)
5)
received
(100
mg)
either
one
or
two
times
day,
placebo
24-week
study
treatment
period.
The
primary
endpoint
was
change
from
baseline
ESSDAI
at
week
24.
Key
secondary
endpoints
included
over
time,
ESSPRI
time
SjS.
exploratory
changes
to
salivary
flow
rate,
soluble
biomarkers,
blood
transcriptomic
serum
proteomic
profiles.
Results
Remibrutinib
significantly
improved
score
SjS
24
weeks
compared
(ΔESSDAI
−2.86,
p=0.003).
No
effect
observed
(ΔESSPRI
0.17,
p=0.663).
There
trend
towards
improvement
unstimulated
weeks.
had
favourable
profile
induced
significant
gene
expression
blood,
protein
abundance
placebo.
Conclusions
These
data
show
preliminary
