medRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Nov. 22, 2023
A
bstract
Pulmonary
hypertension
(PH)
is
a
pathological
condition
that
affects
approximately
1%
of
the
population.
The
prognosis
for
many
patients
poor,
even
after
treatment.
Our
knowledge
about
pathophysiological
mechanisms
cause
or
are
involved
in
progression
PH
incomplete.
Additionally,
mechanism
action
drugs
used
to
treat
pulmonary
hypertension,
including
sotatercept,
requires
elucidation.
Using
our
graph-powered
mining
software
Lifelike
combination
with
very
small
patient
metabolite
data
set,
we
demonstrate
how
derive
detailed
mechanistic
hypotheses
on
pathophysiology
and
clinical
drugs.
In
patients,
concentration
hypoxanthine,
12(S)-HETE,
glutamic
acid,
sphingosine
1
phosphate
significantly
higher,
while
L-arginine
L-histidine
lower
than
healthy
controls.
graph-based
analysis,
gene
ontology,
semantic
association
capabilities
,
led
us
connect
differentially
expressed
metabolites
G-protein
signaling
SRC.
Then,
associated
SRC
IL6
signaling.
Subsequently,
found
associations
SRC,
Activin
BMP
Lastly,
analyzed
several
existing
novel
pharmacological
treatments
PH.
elucidated
interplay
between
G-protein,
interleukin
6,
activin,
Those
pathways
regulate
hallmark
processes
PH,
vasoconstriction,
endothelial
barrier
function,
cell
proliferation,
apoptosis.
results
highlight
importance
ERK1,
AKT,
MLC
activity
molecular
affected
by
also
converge
these
molecules.
Importantly,
sotatercept
simultaneously.
present
study
shows
power
graphs
using
’s
diverse
set
analytics
functionalities
developing
knowledge-driven
drug
their
interactions.
We
believe
presented
approach
will
be
valuable
future
studies
other
diseases,
Therapeutic Advances in Musculoskeletal Disease,
Journal Year:
2024,
Volume and Issue:
16
Published: Jan. 1, 2024
Rheumatoid
arthritis
(RA)
is
an
autoimmune
disease
characterised
by
persistent
inflammation
of
the
synovial
joints
as
well
other
tissues
and
organs.
Left
untreated,
it
can
lead
to
joint
damage,
disability
even
increased
mortality.
The
driven
inflammatory
cytokines
that
contribute
chronic
seen
in
RA.
Interleukin-6
(IL-6)
a
key
pathological
cytokine
target
for
treatments
aiming
alleviate
local
systemic
inflammation.
Despite
advances
understanding
RA
introduction
new
treatments,
achieving
sustained
remission
remains
challenging.
This
review
explores
role
IL-6
pathogenesis,
its
potential
treatment
significance
personalised
medicine
management.
has
dual
signalling
mechanism,
classical
trans-signalling,
which
influences
various
intracellular
pathways.
While
several
targeted
therapies
have
emerged,
no
single
mechanism-based
therapy
universally
effective
due
diversity
complexity
disease.
Different
approaches
targeting
been
tested,
including
biologic
blockade
receptors
or
ligands,
inhibition
signalling.
receptor
inhibitors
validated
therapeutics,
either
alone
combination
with
treatments.
Tocilizumab,
first
approved
inhibitor,
blocks
both
soluble
membrane-bound
receptors,
reducing
cascade.
Clinical
trials
confirm
efficacy
safety
tocilizumab
option
patients
unresponsive
conventional
therapies.
benefits
extend
beyond
reduced
amelioration
comorbidities
like
anaemia,
cardiovascular
disease,
depression
osteoporosis.
Tailoring
patients’
profiles
essential
optimal
outcomes.
A
‘treat-to-profile’
approach,
focusing
on
holistic
view
patient,
could
improve
strategies.
Biosimilars
–
lower-cost
alternatives
biologics
further
enhance
accessibility
cost-effectiveness
treatment.
present
valuable
management,
particularly
specific
comorbidities.
All Life,
Journal Year:
2024,
Volume and Issue:
17(1)
Published: July 1, 2024
Sepsis
is
defined
as
life-threatening
organ
dysfunction
caused
by
a
dysregulated
host
response
to
infection.
It
characterized
high
incidence,
mortality
rate,
and
poor
prognosis.
With
the
increasing
consumption
of
antibiotics
growing
prevalence
antimicrobial
resistance,
clinicians
are
in
greater
need
easily
accessible
effective
inflammatory
markers
monitor
infection
process,
guide
treatment,
assess
patient
Numerous
biomarkers
have
been
studied
for
their
potential
value
diagnosis
sepsis,
more
than
250
different
proposed.
However,
many
these
useful
prognostic
evaluation
diagnosis.
Biomarkers
such
procalcitonin
C-reactive
protein
extensively
studied,
with
being
only
sepsis
biomarker
included
clinical
guidelines.
can
be
used
antibiotic
use
but
should
not
standalone
diagnostic
indicator.
has
sensitivity
specificity
In
recent
years,
new
biomarkers,
neutrophil
extracellular
traps,
interleukin-6,
histones,
cell-free
DNA
composite
indicators,
systemic
immune
inflammation
index,have
identified.
This
article
provides
comprehensive
review
traditional
recently
popular
novel
sepsis.
Journal of Clinical Medicine,
Journal Year:
2024,
Volume and Issue:
13(19), P. 5834 - 5834
Published: Sept. 30, 2024
Precapillary
pulmonary
hypertension
(PH)
is
a
significant
complication
of
systemic
sclerosis
(SSc).
It
represents
one
the
leading
causes
morbidity
and
mortality,
correlating
with
significantly
dismal
prognosis
quality
life.
Despite
advancements
in
management
patients
arterial
associated
SSc
(SSc-PAH),
no
improvement
has
been
reported
survival
precapillary
SSc-PH
extensive
lung
parenchyma
disease.
International
expert
consensus
guidelines
for
PH
recommend
annual
screening
early
detection
pre-capillary
PH.
The
implementation
algorithms
capable
identifying
high
likelihood
developing
could
help
limit
unnecessary
right-heart
catheterization
procedures
prevent
delay
diagnosis.
Furthermore,
initiation
up-front
combination
targeted
therapy
PAH
shown
increase
rates,
indicating
that
timely
aggressive
medical
key
stabilizing
even
improving
functional
class,
hemodynamic
parameters
6
min
walking
distance
(6MWD)
this
population.
Further
research
warranted
into
benefit
PAH-targeted
therapies
Lastly,
we
discuss
potential
role
immunosuppression
using
biologic
agents
therapeutic
patients.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Feb. 14, 2024
Abstract
Identification
of
accurate
biomarkers
is
still
particularly
urgent
for
improving
the
poor
survival
chronic
obstructive
pulmonary
disease
(COPD)
patients.
In
this
investigation,
we
aimed
to
identity
potential
in
COPD
via
bioinformatics
and
next
generation
sequencing
(NGS)
data
analysis.
differentially
expressed
genes
(DEGs)
were
identified
using
NGS
dataset
(GSE239897)
from
Gene
Expression
Omnibus
(GEO)
database.
Subsequently,
gene
ontology
(GO)
pathway
enrichment
analysis
was
conducted
evaluate
underlying
molecular
mechanisms
involved
progression
COPD.
Protein-protein
interaction
(PPI),
modules,
miRNA-hub
regulatory
network
TF-hub
performed
determine
hub
genes,
miRNAs
TFs.
The
receiver
operating
characteristic
(ROC)
diagnostic
value
genes.
A
total
956
overlapping
DEGs
(478
up
regulated
478
down
genes)
dataset.
mainly
associated
with
GO
functional
terms
pathways
cellular
response
stimulus.
stimulus,
immune
system
neutrophil
degranulation.
There
10
(MYC,
LMNA,
VCAM1,
MAPK6,
DDX3X,
SHMT2,
PHGDH,
S100A9,
FKBP5
RPS6KA2)
by
PPI,
conclusion,
DEGs,
relative
terms,
present
investigation
might
aid
understanding
provide
targets
Frontiers in Cardiovascular Medicine,
Journal Year:
2024,
Volume and Issue:
11
Published: May 23, 2024
Introduction
Pulmonary
hypertension
(PH)
is
a
pathological
condition
that
affects
approximately
1%
of
the
population.
The
prognosis
for
many
patients
poor,
even
after
treatment.
Our
knowledge
about
pathophysiological
mechanisms
cause
or
are
involved
in
progression
PH
incomplete.
Additionally,
mechanism
action
drugs
used
to
treat
pulmonary
hypertension,
including
sotatercept,
requires
elucidation.
Methods
Using
our
graph-powered
mining
software
Lifelike
combination
with
very
small
patient
metabolite
data
set,
we
demonstrate
how
derive
detailed
mechanistic
hypotheses
on
pathophysiology
and
clinical
drugs.
Results
In
patients,
concentration
hypoxanthine,
12(S)-HETE,
glutamic
acid,
sphingosine
1
phosphate
significantly
higher,
while
L-arginine
L-histidine
lower
than
healthy
controls.
graph-based
analysis,
gene
ontology,
semantic
association
capabilities
,
led
us
connect
differentially
expressed
metabolites
G-protein
signaling
SRC.
Then,
associated
SRC
IL6
signaling.
Subsequently,
found
associations
SRC,
activin
BMP
Lastly,
analyzed
several
existing
novel
pharmacological
treatments
PH.
elucidated
interplay
between
G-protein,
IL6,
activin,
Those
pathways
regulate
hallmark
processes
PH,
vasoconstriction,
endothelial
barrier
function,
cell
proliferation,
apoptosis.
Discussion
results
highlight
importance
ERK1,
AKT,
MLC
activity
molecular
affected
by
also
converge
these
molecules.
Importantly,
sotatercept
simultaneously.
present
study
shows
power
graphs
using
’s
diverse
set
analytics
functionalities
developing
knowledge-driven
drug
their
interactions.
We
believe
presented
approach
will
be
valuable
future
studies
other
diseases,
International Journal of COPD,
Journal Year:
2023,
Volume and Issue:
Volume 18, P. 2457 - 2471
Published: Nov. 1, 2023
Introduction:
Pulmonary
hypertension
(PH)
is
a
common
complication
of
chronic
obstructive
pulmonary
disease
(COPD),
which
can
worsen
the
prognosis
and
increase
mortality
COPD
patients.
Circular
RNA
(circRNA)
has
been
discovered
to
participate
in
occurrence
progression
PH
may
have
significant
prospects
for
advanced
diagnostics
evaluation.
However,
expression
profile
circRNAs
human
lung
tissues
with
definite
diagnosis
COPD-PH
remains
be
further
explored
validated.
Methods:
Twelve
tissue
samples
(6
each
from
control
groups)
were
collected
subjected
high-throughput
sequencing.
QRT-PCR
was
performed
validate
differential
levels
top
10
dysregulated
patients'
plasma
samples,
HPAECs
HPASMCs.
Functional
pathway
enrichment
analysis
on
target
genes
explore
potential
functions
pathways
those
circRNAs.
Hub
obtained
after
conducting
bioinformatics
predicted
mRNAs
verified
by
qRT-PCR
HPASMCs,
then
we
selected
VCAN
as
key
gene
involved
pathogenesis
immunohistochemistry
validation
tissue.
Results:
A
total
136
(39
up-regulated
97
down-regulated)
differentially
expressed
between
two
groups.
Following
validation,
(hsa_circ_0007608
hsa_circ_0064656)
believed
pathogenesis.
GO
KEGG
suggested
that
these
DECs
mainly
related
celluar
proliferation,
migration
EndMT.
PPI
network
revealed
11
pairs
mRNAs.
VCAM1,
THBS1,
three
hub
highest
reliability
among
all,
validated
proven
COPD-PH.
We
innovatively
found
Conclusion:
This
study
identified
functional
circRNAs,
providing
insights
into
molecular
mechanisms
predictions
COPD-PH,
provide
diagnostic
biomarkers
or
therapeutic
targets
Keywords:
hypertension,
disease,
circular
RNA,
RNA-sequencing,
biomarker,
