Journal of Personalized Medicine,
Год журнала:
2023,
Номер
13(2), С. 366 - 366
Опубликована: Фев. 19, 2023
Pulmonary
vascular
remodeling
is
the
critical
structural
alteration
and
pathological
feature
in
pulmonary
hypertension
(PH)
involves
changes
intima,
media
adventitia.
consists
of
proliferation
phenotypic
transformation
artery
endothelial
cells
(PAECs)
smooth
muscle
(PASMCs)
middle
membranous
artery,
as
well
complex
interactions
involving
external
layer
fibroblasts
(PAFs)
extracellular
matrix
(ECM).
Inflammatory
mechanisms,
apoptosis
other
factors
wall
are
influenced
by
different
mechanisms
that
likely
act
concert
to
drive
disease
progression.
This
article
reviews
these
highlights
some
pathogenetic
involved
process.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Июль 14, 2023
Abstract
Exposure
to
the
spike
protein
or
receptor-binding
domain
(S-RBD)
of
SARS-CoV-2
significantly
influences
endothelial
cells
and
induces
pulmonary
vascular
endotheliopathy.
In
this
study,
angiotensin-converting
enzyme
2
humanized
inbred
(hACE2
Tg)
mice
cultured
were
used
investigate
how
protein/S-RBD
impacts
endothelium.
Results
show
that
S-RBD
leads
acute-to-prolonged
induction
intracellular
free
calcium
concentration
([Ca
2+
]
i
)
via
acute
activation
TRPV4,
prolonged
upregulation
mechanosensitive
channel
Piezo1
store-operated
(SOCC)
key
component
Orai1
in
human
arterial
(PAECs).
mechanism,
interacts
with
ACE2
induce
formation
clusters
involving
Orai1,
TRPC1,
facilitate
SOCC,
lead
elevated
apoptosis.
These
effects
are
blocked
by
Kobophenol
A,
which
inhibits
binding
between
ACE2,
chelator,
BAPTA-AM.
Blockade
SOCC
GsMTx4
effectively
protects
S-RBD-induced
microvascular
damage
hACE2
Tg
normalizing
[Ca
.
Comparing
prototypic
strain,
Omicron
variants
(BA.5.2
XBB)
less
severe
cell
Transcriptomic
analysis
indicates
confers
more
than
Delta
Lambda
S-RBD.
summary,
study
provides
compelling
evidence
could
persistent
triggering
through
Orai1.
Targeted
inhibition
ACE2-Piezo1/SOCC-[Ca
axis
proves
a
powerful
strategy
treat
diseases.
Abstract
The
gut
microbiota
is
a
complex
community
of
microorganisms
inhabiting
the
intestinal
tract,
which
plays
vital
role
in
human
health.
It
intricately
involved
metabolism,
and
it
also
affects
diverse
physiological
processes.
gut–lung
axis
bidirectional
pathway
between
gastrointestinal
tract
lungs.
Recent
research
has
shown
that
microbiome
crucial
immune
response
regulation
lungs
development
lung
diseases.
In
this
review,
we
present
interrelated
factors
concerning
associated
metabolites
pulmonary
hypertension
(PH),
lethal
disease
characterized
by
elevated
vascular
pressure
resistance.
Our
team
explored
gut‐microbiota‐derived
cardiovascular
diseases
established
correlation
such
as
putrescine,
succinate,
trimethylamine
N‐oxide
(TMAO),
N,
N‐trimethyl‐5‐aminovaleric
acid
with
Furthermore,
found
specific
metabolites,
TMAO
betaine,
have
significant
clinical
value
PH,
suggesting
their
potential
biomarkers
management.
detailing
interplay
microbiota,
underscored
therapeutic
approaches
modulating
microbiota.
Ultimately,
endeavor
to
alleviate
substantial
socioeconomic
burden
disease.
This
review
presents
unique
exploratory
analysis
link
intending
propel
further
investigations
axis.
The
association
between
lung
microbiome
and
pulmonary
hypertension
(PH)
remain
unknown.
This
study
aims
to
define
the
airway
mycobiome
signature
its
potential
correlation
with
clinical
parameters
of
PH.
Overall,
244
patients
PH
120
healthy
controls
(CON)
were
recruited
from
three
independent
centers.
group
was
divided
into
subgroups
not
using
antibiotics
or
corticosteroids
(non-ANT/CORT),
those
ANT,
CORT,
ANT
+
CORT
within
1
month,
classification
(Groups
1,
3,
4),
World
Health
Organization
functional
class
(I–IV),
disease
severity
based
on
mean
artery
pressure
vascular
resistance
levels
for
in-depth
comparison.
Distinct
profiles
observed
in
PH,
CON,
subgroups.
Linear
discriminant
analysis
effect
size
showed
increased
Purpureocillium,
Issatchenkia,
Cyberlindnera
decreased
Peroneutypa,
Simplicillium,
Metarhizium
(non-ANT/CORT,
CORT)
than
CON.
Receiver
operating
characteristic
indicated
a
strong
prediction
two
fungal
genera
sets
distinguishing
major
phyla,
Ascomycota
Basidiomycota,
correlated
differently
factors.
Increased
connections
among
top
phyla
CON
group.
Dominant
enrichment
(Purpureocillium,
Cyberlindnera)
diminishment
(Peroneutypa,
Metarhizium)
consistently
strongly
predicted
without
being
influenced
by
different
provides
first
description
unique
Supramolecular Materials,
Год журнала:
2023,
Номер
2, С. 100043 - 100043
Опубликована: Окт. 12, 2023
Ion
channels
play
a
vital
role
in
regulating
the
flow
of
ions
across
cell
membranes
to
maintain
physiological
functions.
Mimicking
this
biological
process
and
fabricating
artificial
nano-/micro-channels
with
similar
functions
are
expected
solve
challenges
involving
ion
transport
fields
such
as
energy,
environment,
human
health.
As
flexible
controllable
preparation
technology,
supramolecular
self-assembly
is
powerful
tool
for
designing
biomimetic
specific
purposes.
Although
various
have
been
reported,
ever-increasing
research
interest
their
application
potential
call
bridge
between
design
principles
engineering
applications.
In
Perspective,
we
summarized
recent
advances
new
field
analyzed
working
mechanism
based
on
grounded
theory
chemistry
nanofluidic
systems.
To
promote
progress
field,
opportunities
key
future
applications
highlighted.
BACKGROUND
Pulmonary
hypertension
(PH)
is
a
progressive
disorder
characterized
by
elevated
pulmonary
artery
pressure
and
increased
vascular
resistance,
ultimately
leading
to
right
heart
failure.
Early
detection
critical
for
improving
patient
outcomes.
OBJECTIVE
To
establish
novel
machine
learning-based
diagnostic
model
PH.
METHODS
A
the
early
of
was
developed
through
two-step
approach.
First,
Recursive
Feature
Elimination
(RFE)
employed
select
most
relevant
echocardiographic
variables,
which
were
subsequently
integrated
into
composite
ultrasound
index
using
learning
techniques
such
as
XGBoost.
In
second
step,
this
with
clinical
variables
identified
LASSO
regression.
Together,
these
elements
combined
construct
logistic
regression
diagnosis.
The
model’s
performance
rigorously
evaluated
ROC
curves,
calibration
plots,
decision
curve
analysis
(DCA)
ensure
its
relevance
accuracy.
RESULTS
Machine
key
predictors,
XGBoost
achieving
high
AUC,
sensitivity,
specificity.
including
prothrombin
time
activity
serum
cystatin
C.
demonstrated
predictive
accuracy,
an
AUC
0.997.
Calibration
analyses
indicated
close
alignment
between
predicted
observed
outcomes
validating
value,
especially
at
higher
risk
thresholds.
CONCLUSIONS
This
enhances
diagnosis
non-invasive
approach
demonstrates
strong
It
facilitates
intervention
personalized
treatment,
potential
applications
in
broader
cardiovascular
disease
management.
CLINICALTRIAL
study
approved
Research
Ethics
Commission
Wuhan
Zhongnan
Hospital
requirement
informed
consent
waived
(Approval
No.2023185)
BACKGROUND:
Pulmonary
hypertension
of
the
newborn
is
a
life-threatening
disorder
characterized
by
elevated
pulmonary
vascular
resistance
due
to
maladaptation
circulation
after
birth.
The
etiology
and
mechanisms
underlying
remain
unclear,
hindering
development
effective
treatment.
We
hypothesize
that
perinatal
chronic
hypoxia
upregulates
microRNA-210,
which
essential
for
suppression
arterial
spontaneous
transient
outward
currents
(STOCs),
resulting
in
newborn.
METHODS:
tested
this
hypothesis
large
animal
model
pregnant
sheep
lambs
exposed
comparing
loss-
versus
gain-of-function
microRNA-210.
RESULTS:
Chronic
increases
pressure
lambs.
effect
was
mainly
mediated
birth
Mechanistically,
we
showed
significant
decrease
microRNA-210
arteries
birth,
but
abolished
birth-induced
reduction.
found
mimic
suppressed
STOCs
arteries,
knockdown
microRNA-210-LNA
prevented
hypoxia-induced
reduction
STOCs.
In
vivo
loss-of-function
experiments
reveal
STOCs,
increased
resistance,
via
downregulation
iron-sulfur
cluster
assembly
enzyme
large-conductance
Ca
2+
-activated
K
+
channels.
CONCLUSIONS:
provide
explicit
evidence
neonatal
expression,
Our
study
reveals
new
insights
into
clinically
meaningful
targets
treatment
