Frontiers in Pharmacology,
Год журнала:
2019,
Номер
10
Опубликована: Апрель 2, 2019
Non
resolving
inflammation
is
the
main
mechanism
of
morbidity
and
mortality
among
patients
suffering
from
cystic
fibrosis
(CF),
most
common
life-threatening
human
genetic
disease.
Resolution
an
active
process
timely
controlled
by
endogenous
specialized
pro-resolving
lipid
mediators
(SPM)
produced
locally
in
inflammatory
loci
to
curtail
this
innate
response,
prevent
further
damages
host,
permit
return
homeostasis.
Lipoxins,
resolvins,
protectins,
maresins
are
SPM
derived
polyunsaturated
fatty
that
limit
excessive
leukocyte
infiltration
pro-inflammatory
signals,
stimulate
microbial
killing,
enhance
resolution
Their
unique
chemical
structures,
receptors,
bioactions
being
elucidated.
Accruing
data
indicate
carry
protective
functions
against
unrelenting
infections
preclinical
models
CF
systems.
Here,
we
reviewed
their
roles
actions
controlling
inflammation,
evidence
for
impairment
CF,
proofs
principle
exploitation
as
innovative,
non
immunosuppressive,
drugs
address
CF.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Фев. 8, 2023
Abstract
We
are
currently
witnessing
transformative
change
for
people
with
cystic
fibrosis
the
introduction
of
small
molecule,
mutation-specific
drugs
capable
restoring
function
defective
protein,
transmembrane
conductance
regulator
(CFTR).
However,
despite
being
a
single
gene
disorder,
there
multiple
fibrosis-causing
genetic
variants;
not
suitable
all
variants
and
also
do
correct
multisystem
clinical
manifestations
disease.
For
many,
will
remain
need
improved
treatments.
Those
patients
responsive
to
CFTR
modulators
may
have
found
these
therapies
be
transformational;
research
is
now
focusing
on
safely
reducing
burden
symptom-directed
treatment.
available
in
parts
globe,
an
issue
which
further
widening
existing
health
inequalities.
who
for-
or
access
to-
modulator
drugs,
alternative
approaches
progressing
through
trials
pipeline.
There
challenges
encountered
design
implementation
trials,
established
global
CF
infrastructure
major
advantage.
Here,
Cystic
Fibrosis
National
Research
Strategy
Group
UK
NIHR
Respiratory
Translational
Collaboration
looks
future
consider
priorities
development.
Frontiers in Molecular Biosciences,
Год журнала:
2024,
Номер
10
Опубликована: Янв. 8, 2024
Exhaled
breath
analysis,
with
particular
emphasis
on
volatile
organic
compounds,
represents
a
growing
area
of
clinical
research
due
to
its
obvious
advantages
over
other
diagnostic
tests.
Numerous
pathologies
have
been
extensively
investigated
for
the
identification
specific
biomarkers
in
exhalates
through
metabolomics.
However,
transference
tests
clinics
remains
limited,
mainly
deficiency
methodological
standardization.
Critical
steps
include
selection
sample
types,
collection
devices,
and
enrichment
techniques.
GC-MS
is
reference
analytical
technique
analysis
compounds
exhalates,
especially
during
biomarker
discovery
phase
This
review
comprehensively
examines
compares
metabolomic
studies
focusing
cancer,
lung
diseases,
infectious
diseases.
In
addition
delving
into
experimental
designs
reported,
it
also
provides
critical
discussion
aspects,
ranging
from
design
potential
pathology-specific
biomarkers.
Thorax,
Год журнала:
2019,
Номер
74(7), С. 684 - 692
Опубликована: Фев. 18, 2019
Recent
studies
of
human
respiratory
secretions
using
culture-independent
techniques
have
found
a
surprisingly
diverse
array
microbes.
Interactions
among
these
community
members
can
profoundly
impact
microbial
survival,
persistence
and
antibiotic
susceptibility
and,
consequently,
disease
progression.
Studies
polymicrobial
interactions
in
the
microbiota
shown
that
taxonomic
structural
compositions,
resulting
behaviours,
communities
differ
substantially
from
those
individual
constituent
species
ways
clinical
importance.
These
primarily
involved
oral
gastrointestinal
microbiomes.
While
field
is
relatively
young,
early
findings
suggest
tract
also
compete
cooperate
may
influence
outcomes.
Ongoing
efforts
therefore
focus
on
how
inform
more
‘enlightened’,
rational
approaches
to
combat
infections.
Among
most
common
diseases
involving
infections
are
cystic
fibrosis
(CF),
non-CF
bronchiectasis,
COPD
ventilator-associated
pneumonia.
be
diverse,
two
best-studied
Staphylococcus
aureus
Pseudomonas
aeruginosa
,
which
exhibit
range
competitive
cooperative
interactions.
Here,
we
review
state
research
pulmonary
coinfection
with
pathogens,
including
their
prevalence,
combined
independent
associations
patient
outcomes,
mechanisms
could
lung
health.
Because
P.
aeruginosa–S.
well
studied
CF,
this
serves
as
paradigm
for
our
discussions
organisms
recommendations
future
disease.
Genes,
Год журнала:
2019,
Номер
10(3), С. 183 - 183
Опубликована: Фев. 26, 2019
Genetic
defects
in
cystic
fibrosis
(CF)
transmembrane
conductance
regulator
(CFTR)
gene
cause
CF.
Infants
with
CFTR
mutations
show
a
peribronchial
neutrophil
infiltration
prior
to
the
establishment
of
infection
their
lung.
The
inflammatory
response
progressively
increases
children
that
include
both
upper
and
lower
airways.
Infectious
leads
an
increase
mucus
viscosity
plugging
small
medium-size
bronchioles.
Eventually,
neutrophils
chronically
infiltrate
airways
biofilm
or
chronic
bacterial
infection.
Perpetual
airway
inflammation
destroy
lungs,
which
increased
morbidity
eventual
mortality
most
patients
Studies
have
now
established
cytotoxins,
extracellular
DNA,
traps
(NETs)
are
associated
clogging
lung
injury
In
addition
opportunistic
pathogens,
various
aspects
CF
milieux
(e.g.,
pH,
salt
concentration,
phenotypes)
influence
NETotic
capacity
neutrophils.
milieu
may
promote
survival
pro-inflammatory
aberrant
NETosis,
rather
than
anti-inflammatory
apoptotic
death
these
cells.
Degrading
NETs
helps
manage
disease;
since
DNAse
treatment
release
cytotoxins
from
NETs,
further
improvements
needed
degrade
maximal
positive
effects.
Neutrophil-T
cell
interactions
be
important
regulating
viral
infection-mediated
pulmonary
exacerbations
infections.
Therefore,
clarifying
role
disease
identifying
therapies
preserve
effects
neutrophils,
while
reducing
detrimental
cytotoxic
components,
essential
achieving
innovative
therapeutic
advances.
International Journal of Molecular Sciences,
Год журнала:
2020,
Номер
21(10), С. 3708 - 3708
Опубликована: Май 25, 2020
Pulmonary
surfactant
is
a
lipid/protein
complex
synthesized
by
the
alveolar
epithelium
and
secreted
into
airspaces,
where
it
coats
protects
large
respiratory
air–liquid
interface.
Surfactant,
assembled
as
network
of
membranous
structures,
integrates
elements
in
charge
reducing
surface
tension
to
minimum
along
breathing
cycle,
thus
maintaining
open
gas
exchange
also
protecting
lung
body
from
entrance
myriad
potentially
pathogenic
entities.
Different
molecules
establish
multivalent
crosstalk
with
epithelium,
immune
system
microbiota,
constituting
crucial
platform
sustain
homeostasis,
under
health
disease.
This
review
summarizes
some
most
important
interactions
within
how
multiple
lipid–protein
protein–protein
contribute
proper
maintenance
an
operative
surface.
American Journal of Respiratory and Critical Care Medicine,
Год журнала:
2019,
Номер
200(11), С. 1381 - 1391
Опубликована: Авг. 27, 2019
Rationale:
Cystic
fibrosis
(CF)
pulmonary
disease
is
characterized
by
chronic
infection
with
Pseudomonas
aeruginosa
and
sustained
neutrophil-dominant
inflammation.
The
lack
of
effective
antiinflammatory
therapies
for
people
CF
(PWCF)
represents
a
significant
challenge.Objectives:
To
identify
altered
immunometabolism
in
the
neutrophil
investigate
feasibility
specific
inhibition
NLRP3
(NOD-,
LRR-,
pyrin
domain–containing
protein
3)
inflammasome
as
strategy
vivo.Methods:
Key
markers
increased
aerobic
glycolysis,
known
Warburg
effect,
including
cytosolic
PKM2
(pyruvate
kinase
M2),
phosphorylated
PKM2,
succinate,
HIF-1α
(hypoxia-inducible
factor-1α),
lactate,
IL-1β
precursor
pro–IL-1β,
well
caspase-1
activity
processing
pro–IL-1β
to
inflammasome,
were
measured
neutrophils
from
blood
airway
secretions
healthy
control
subjects
(n
=
12),
PWCF
16),
after
double-lung
transplantation
6).
effects
on
inflammation
bacterial
clearance
murine
model
subsequently
assessed
vivo.Measurements
Main
Results:
display
glycolysis
systemic
circulation.
This
effect
driven
low-level
endotoxemia,
unaffected
CFTR
(cystic
transmembrane
conductance
regulator)
modulation,
resolves
transplant.
produced
processed
its
mature
active
form
LPS-rich
lung
via
caspase-1.
Specific
vivo
MCC950
inhibited
lungs
mice
(P
<
0.0001),
resulting
significantly
reduced
improved
0.0001).Conclusions:
response
may
have
an
anti-infective
role
CF.
Cells,
Год журнала:
2021,
Номер
10(11), С. 2844 - 2844
Опубликована: Окт. 22, 2021
Cystic
fibrosis
(CF)
is
a
recessive
genetic
disease
caused
by
mutations
in
gene
encoding
protein
called
Fibrosis
Transmembrane
Conductance
Regulator
(CFTR).
The
CFTR
known
to
acts
as
chloride
(Cl-)
channel
expressed
the
exocrine
glands
of
several
body
systems
where
it
also
regulates
other
ion
channels,
including
epithelial
sodium
(Na+)
(ENaC)
that
plays
key
role
salt
absorption.
This
function
crucial
osmotic
balance
mucus
and
its
viscosity.
However,
pathophysiology
CF
more
challenging
than
mere
dysregulation
transport,
mainly
resulting
impaired
mucociliary
clearance
(MCC)
with
consecutive
bronchiectasis
pancreatic
insufficiency.
review
shows
not
just
channel.
For
long
time,
research
has
focused
on
abnormal
Cl-
Na+
transport.
Yet,
numerous
pathways,
such
transport
HCO3-,
glutathione
thiocyanate,
immune
cells,
metabolism
lipids.
It
influences
pH
homeostasis
airway
surface
liquid
thus
MCC
well
innate
immunity
leading
chronic
infection
inflammation,
all
which
are
considered
pathophysiological
characteristics
CF.
Mucosal Immunology,
Год журнала:
2020,
Номер
14(2), С. 282 - 295
Опубликована: Ноя. 12, 2020
Airway
macrophages
(AMs)
play
key
roles
in
the
maintenance
of
lung
immune
tolerance.
Tissue
tailored,
highly
specialised
and
strategically
positioned,
AMs
are
critical
sentinels
homoeostasis.
In
last
decade,
there
has
been
a
revolution
our
understanding
how
metabolism
underlies
macrophage
functions.
While
these
initial
observations
were
made
during
steady
state
or
using
vitro
polarised
macrophages,
recent
studies
have
indicated
that
many
chronic
diseases
(CLDs),
adapt
their
metabolic
profile
to
fit
local
niche.
By
generating
reactive
oxygen
species
(ROS)
for
pathogen
defence,
utilising
aerobic
glycolysis
rapidly
generate
cytokines,
employing
mitochondrial
respiration
fuel
inflammatory
responses,
utilise
reprogramming
host
although
changes
may
also
support
pathology.
This
review
focuses
on
alterations
underlie
AM
phenotype
function
CLDs.
Particular
emphasis
is
given
new
plasticity
be
exploited
develop
AM-focused
therapies.