ACS Infectious Diseases,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 21, 2025
Human
oxysterol-binding
protein
(OSBP)
is
a
potentially
druggable
mediator
in
the
replication
of
broad
spectrum
positive-sense
(+)
single-stranded
RNA
(ssRNA)
viruses,
including
members
Picornaviridae,
Flaviviridae,
and
Coronaviridae.
OSBP
cytoplasmic
lipid
transporting
capable
moving
cholesterol
phosphoinositides
between
endoplasmic
reticulum
(ER)
Golgi,
ER
lysosome.
Several
structurally
diverse
antiviral
compounds
have
been
reported
to
function
through
targeting
OSBP,
natural
product
compound
OSW-1.
Our
prior
work
shows
that
transient
OSW-1
treatment
induces
reduction
levels
over
multiple
successive
cell
generations
(i.e.,
multigenerational),
with
no
apparent
cellular
toxicity,
OSW-1-induced
has
activity
against
(+)ssRNA
viruses.
This
study
extends
these
findings
establishes
vitro
pathogenic
human
rhinovirus
(HRV1B),
feline
coronavirus
peritonitis
virus
(FIPV),
229E
(HCoV-229E),
severe
acute
respiratory
syndrome
2
(SARS-CoV-2).
We
also
demonstrate
airway
epithelial
cells
alters
expression
innate
immune
mediators,
interferon
(IFN)
related
genes
IFNB1,
IFNL3,
CXCL10,
ISG15,
MX1.
Furthermore,
enhances
induction
specific
components
type
I
III
IFN
responses
triggered
by
viral
mimetic
polyinosinic-polycytidylic
acid
(Poly
IC).
In
summary,
this
further
demonstrates
importance
presents
as
potential
regulator
responses.
Cells,
Journal Year:
2024,
Volume and Issue:
13(2), P. 123 - 123
Published: Jan. 9, 2024
The
COVID-19
pandemic
has
brought
to
the
forefront
intricate
relationship
between
SARS-CoV-2
and
its
impact
on
neurological
complications,
including
potential
links
neurodegenerative
processes,
characterized
by
a
dysfunction
of
protein
quality
control
systems
ER
stress.
This
review
article
explores
role
systems,
such
as
Unfolded
Protein
Response
(UPR),
Endoplasmic
Reticulum-Associated
Degradation
(ERAD),
Ubiquitin–Proteasome
System
(UPS),
autophagy
molecular
chaperones,
in
infection.
Our
hypothesis
suggests
that
produces
stress
exploits
leading
disruption
proteostasis
cannot
be
solved
host
cell.
culminates
cell
death
may
represent
link
neurodegeneration.
mBio,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 20, 2024
ABSTRACT
Interferons
(IFNs)
are
multifaceted
proteins
that
play
pivotal
roles
in
orchestrating
robust
antiviral
immune
responses
and
modulating
the
intricate
landscape
of
host
immunity.
The
major
signaling
pathway
activated
by
IFNs
is
JAK/STAT
(Janus
kinase/signal
transducer
activator
transcription)
pathway,
which
leads
to
transcription
a
battery
genes,
collectively
known
as
IFN-stimulated
genes
(ISGs).
While
well-established
role
coordinating
innate
response
against
viral
infections
widely
acknowledged,
recent
years
have
provided
more
distinct
comprehension
functional
significance
attributed
non-canonical,
IFN-independent
induction
ISGs.
In
this
review,
we
summarize
non-conventional
pathways
ISG
induction.
These
alternative
offer
new
avenues
for
developing
strategies
or
immunomodulation
various
diseases.
Molecular Biology and Evolution,
Journal Year:
2024,
Volume and Issue:
41(3)
Published: Feb. 20, 2024
Viruses
represent
a
major
threat
to
all
animals,
which
defend
themselves
through
induction
of
large
set
virus-stimulated
genes
that
collectively
control
the
infection.
In
vertebrates,
these
include
interferons
play
critical
role
in
amplification
response
Virus-
and
interferon-stimulated
restriction
factors
targeting
different
steps
viral
replication
cycle,
addition
molecules
associated
with
inflammation
adaptive
immunity.
Predictably,
antiviral
evolve
dynamically
pressure.
As
result,
each
animal
has
unique
arsenal
genes.
Here,
we
exploit
capacity
experimentally
activate
evolutionarily
conserved
stimulator
IFN
(STING)
signaling
pathway
by
injection
cyclic
dinucleotide
2'3'-cyclic
guanosine
monophosphate-adenosine
monophosphate
into
flies
define
repertoire
STING-regulated
10
Drosophila
species,
spanning
40
million
years
evolution.
Our
data
reveal
factors,
including
STING
itself,
cGAS-like-receptor,
factor
pastel,
protein
Vago,
but
also
2
key
components
RNA
interference
pathway,
Dicer-2,
Argonaute2.
addition,
identify
unknown
species-
or
lineage-specific
have
not
been
previously
resistance
viruses.
provide
insight
core
pave
way
for
characterization
effectors.
Cell Death Discovery,
Journal Year:
2024,
Volume and Issue:
10(1)
Published: March 6, 2024
Abstract
Serine
protease
inhibitor
clade
E
member
1
(SERPINE1)
inhibits
extracellular
matrix
proteolysis
and
cell
detachment.
However,
SERPINE1
expression
also
promotes
tumor
progression
plays
a
crucial
role
in
metastasis.
Here,
we
solve
this
apparent
paradox
report
that
Serpine1
mRNA
per
se,
independent
of
its
protein-coding
function,
confers
mesenchymal
properties
to
the
cell,
promoting
migration,
invasiveness,
resistance
anoikis
increasing
glycolytic
activity
by
sequestering
miRNAs.
Expression
upregulates
TRA2B
splicing
factor
without
affecting
levels.
Through
transcriptional
profiling,
found
downregulates
through
genes
involved
immune
response.
Analysis
human
colon
samples
showed
an
inverse
correlation
between
CD8+
T
infiltration,
unveiling
potential
value
as
promising
therapeutic
target
for
tumors.
Cells,
Journal Year:
2025,
Volume and Issue:
14(6), P. 400 - 400
Published: March 9, 2025
Pulmonary
homeostasis
can
be
agitated
either
by
external
environmental
insults
or
endogenous
factors
produced
during
respiratory/pulmonary
diseases.
The
lungs
counter
these
initiating
mechanisms
of
inflammation
as
a
localized,
non-specific
first-line
defense
response.
Cytokines
are
small
signaling
glycoprotein
molecules
that
control
the
immune
They
formed
numerous
categories
cell
types
and
induce
movement,
growth,
differentiation,
death
cells.
During
respiratory
diseases,
multiple
proinflammatory
cytokines
play
crucial
role
in
orchestrating
chronic
structural
changes
tract
recruiting
inflammatory
cells
maintaining
release
growth
to
maintain
inflammation.
issue
aggravates
when
response
is
exaggerated
and/or
cytokine
production
becomes
dysregulated.
In
such
instances,
unresolving
reactions
accelerate
airway
remodeling
maladaptive
outcomes.
Pro-inflammatory
generate
deleterious
consequences
through
interactions
with
receptors,
which
turn
initiate
signal
cell,
triggering
profile
cascade
seen
different
pulmonary
diseases
vary
have
become
fundamental
targets
for
advancement
new
therapeutic
strategies
lung
There
considerable
approaches
target
cytokine-mediated
diseases;
however,
blocking
specific
may
not
contribute
clinical
benefit.
Alternatively,
broad-spectrum
anti-inflammatory
more
likely
clinically
effective.
Herein,
this
comprehensive
review
literature
identifies
various
(e.g.,
interleukins,
chemokines,
factors)
involved
pathogenesis
asthma,
obstructive
pulmonary,
cancer,
pneumonia,
fibrosis)
investigates
targeted
treatment
approaches.
ABSTRACT
Background
Three
Janus
kinase
(JAK)
inhibitors
are
approved
for
ulcerative
colitis
(UC)
in
Japan.
Aim
To
compare
the
real‐world
efficacy
and
safety
of
these
three
JAK
UC.
Methods
This
was
a
multicentre,
retrospective
study
patients
with
UC
started
on
inhibitors.
The
primary
outcome
clinical
remission
at
10,
26
58
weeks,
most
recent
follow‐up.
among
inhibitors,
we
created
matched
cohorts
(upadacitinib
vs.
filgotinib,
tofacitinib
filgotinib
upadacitinib
tofacitinib)
using
propensity
score
matching.
Results
We
identified
228
upadacitinib‐treated
(median
follow‐up
49
weeks;
IQR
25–72),
215
filgotinib‐treated
(follow‐up
56
17–82)
159
tofacitinib‐treated
112
10–258).
Clinical
rates
upadacitinib,
were
72.8%,
50.6%
45.8%,
respectively.
Over
70%
previously
treated
other
biologics
or
achieved
upadacitinib.
On
multivariate
analysis,
number
previous
advanced
therapies
inversely
associated
tofacitinib.
Comparative
analysis
showed
that
had
higher
lower
risk
discontinuation
than
However,
significant
acne.
Conclusions
Considering
particularly
high
even
refractory
UC,
may
be
considered
as
an
upfront
inhibitor
before
Viruses,
Journal Year:
2024,
Volume and Issue:
16(2), P. 212 - 212
Published: Jan. 31, 2024
Viruses
evolve
many
strategies
to
ensure
the
efficient
synthesis
of
their
proteins.
One
such
strategy
is
inhibition
integrated
stress
response—the
mechanism
through
which
infected
cells
arrest
translation
phosphorylation
alpha
subunit
eukaryotic
initiation
factor
2
(eIF2α).
We
have
recently
shown
that
human
common
cold
betacoronavirus
OC43
actively
inhibits
eIF2α
in
response
sodium
arsenite,
a
potent
inducer
oxidative
stress.
In
this
work,
we
examined
modulation
responses
by
and
demonstrated
negative
feedback
regulator
GADD34
strongly
induced
cells.
However,
upregulation
expression
was
independent
from
activation
not
required
for
virus-infected
Our
work
reveals
complex
interplay
between
coronavirus
response,
viral
protein
ensured
but
loop
disrupted.
Cell Reports,
Journal Year:
2024,
Volume and Issue:
43(9), P. 114678 - 114678
Published: Aug. 27, 2024
Viruses
pose
a
significant
threat
to
cellular
organisms.Innate
antiviral
immunity
encompasses
both
RNA-and
protein-based
mechanisms
designed
sense
and
respond
infections,
fundamental
aspect
present
in
all
living
organisms.A
potent
RNA-based
mechanism
is
RNA
interference,
where
small
RNA-programmed
nucleases
target
viral
RNAs.Protein-based
often
rely
on
the
induction
of
transcriptional
responses
triggered
by
recognition
infections
through
innate
immune
receptors.These
involve
upregulation
genes
aimed
at
countering
infections.In
this
review,
we
delve
into
recent
advances
understanding
diversification
animals.An
evolutionary
perspective
gains
losses
diverse
animals
coupled
mechanistic
studies
model
organisms
such
as
fruit
fly
Drosophila
melanogaster
essential
provide
deep
that
can
be
translated
new
strategies
treatment
diseases.