bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 6, 2024
ABSTRACT
Streptococcus
pneumoniae
(
Sp
;
pneumococcus),
the
most
common
agent
of
community-acquired
pneumonia,
can
spread
systemically,
particularly
in
elderly,
highlighting
need
for
adjunctive
therapies.
The
airway
epithelial
barrier
defends
against
bacteremia
and
is
dependent
upon
apical
junctional
complex
(AJC)
proteins
such
as
E-cadherin.
After
mouse
lung
challenge,
pneumolysin
(PLY),
a
key
virulence
factor,
stimulates
secretion
an
inflammatory
eicosanoid,
triggering
infiltration
polymorphonuclear
leukocytes
(PMNs)
that
secrete
high
levels
neutrophil
elastase
(NE),
thus
promoting
damage
systemic
infection.
Here,
pulmonary
E-cadherin
staining
intratracheally
inoculated
mice
revealed
PLY-mediated
disruption
AJC
independently
PMNs.
Apical
infection
air-liquid
interface
(ALI)
respiratory
monolayers
similarly
showed
PLY
disrupts
AJCs.
This
promoted
PMN
transmigration
bacterial
apical-to-basolateral
translocation,
pharmacologically
fortifying
function
diminished
both
breach
vitro
vivo
.
after
intratracheal
inoculation
>20-month-old
mice,
or
ALI
derived
from
these
age-associated
vulnerability
to
disruption,
which
turn
enhanced
migration
bacteremia.
In
addition,
we
found
PMNs
aged
increased
tissue-damaging
NE.
Simultaneous
pharmacological
inhibition
tissue-destructive
NE
fortification
was
required
reduce
level
young
mice.
work
underscores
importance
fully
characterizing
multifactorial
sources
susceptibility
devising
therapies
mitigate
invasive
pneumococcal
disease
elderly.
This
review
highlights
recent
progress
in
exosome-based
drug
delivery
for
cancer
therapy,
covering
exosome
biogenesis,
cargo
selection
mechanisms,
and
their
application
across
multiple
types.
As
small
extracellular
vesicles,
exosomes
exhibit
high
biocompatibility
low
immunogenicity,
making
them
ideal
vehicles
capable
of
efficiently
targeting
cells,
minimizing
off-target
damage
side
effects.
aims
to
explore
the
potential
with
a
focus
on
applications
chemotherapy,
gene
immunomodulation.
Additionally,
challenges
related
production
standardization
are
analyzed,
highlighting
importance
addressing
these
issues
clinical
application.
In
conclusion,
systems
offer
promising
future
therapies.
Further
research
should
aim
enhance
efficiency
facilitate
translation,
paving
way
innovative
treatment
strategies.
Frontiers in Microbiology,
Год журнала:
2024,
Номер
15
Опубликована: Июль 16, 2024
Preclinical
evidence
has
firmly
established
a
bidirectional
interaction
among
the
lung,
gut,
and
gut
microbiome.
There
are
many
complex
communication
pathways
between
lung
intestine,
which
affect
each
other's
balance.
Some
metabolites
produced
by
intestinal
microorganisms,
immune
cells,
factors
enter
tissue
through
blood
circulation
participate
in
function.
Altered
gut-lung-microbiome
interactions
have
been
identified
rodent
models
humans
of
several
diseases
such
as
pulmonary
fibrosis,
chronic
obstructive
disease,
cancer,
asthma,
etc.
Emerging
suggests
that
microbial
therapies
can
prevent
treat
respiratory
diseases,
but
it
is
unclear
whether
this
association
simple
correlation
with
pathological
mechanisms
disease
or
result
causation.
In
review,
we
summarize
critical
link
microbiota
well
influence
mechanism
on
discuss
role
interventions
prebiotics
fecal
bacteria
transplantation
diseases.
To
provide
reference
for
rational
design
large-scale
clinical
studies,
direct
application
therapy
to
respiratory-related
reduce
incidence
severity
accompanying
complications.
Infectious Disease Reports,
Год журнала:
2024,
Номер
16(6), С. 1127 - 1181
Опубликована: Ноя. 28, 2024
Background:
Phage
therapy,
a
treatment
utilizing
bacteriophages
to
combat
bacterial
infections,
is
gaining
attention
as
promising
alternative
antibiotics,
particularly
for
managing
antibiotic-resistant
bacteria.
This
study
aims
provide
comprehensive
review
of
phage
therapy
by
examining
its
safety,
efficacy,
influencing
factors,
future
prospects,
and
regulatory
considerations.
The
also
seeks
identify
strategies
optimizing
application
propose
systematic
framework
clinical
implementation.
Methods:
A
analysis
preclinical
studies,
trials,
frameworks
was
undertaken
evaluate
the
therapeutic
potential
therapy.
included
an
in-depth
assessment
key
factors
outcomes,
such
infection
site,
phage–host
specificity,
burden,
immune
response.
Additionally,
innovative
strategies—such
combination
therapies,
bioengineered
phages,
cocktails—were
explored
enhance
efficacy.
Critical
considerations
related
dosing,
including
inoculum
size,
multiplicity
infection,
windows,
personalized
medicine
approaches,
were
examined
optimize
outcomes.
Results:
has
demonstrated
favorable
safety
profile
in
both
settings,
with
minimal
adverse
effects.
Its
ability
specifically
target
harmful
bacteria
while
preserving
beneficial
microbiota
underpins
efficacy
treating
range
infections.
However,
variable
outcomes
some
studies
highlight
importance
addressing
critical
that
influence
success.
Innovative
expanded
access
diverse
banks,
cocktails,
medicine,
hold
significant
promise
improving
Optimizing
dosing
remains
area
enhancement,
kinetics,
resistance
potential,
frequency,
patient-specific
factors.
To
support
streamlined
four-step
guideline
been
developed,
providing
effective
planning
Conclusion:
offers
highly
adaptable,
targeted,
cost-effective
approach
While
several
must
be
thoroughly
evaluated
there
improvement
through
refined
methodologies.
Although
yet
achieve
widespread
approval
U.S.
Europe,
accessibility
Expanded
Access
programs
FDA
authorizations
food
pathogen
control
underscores
promise.
Established
practices
countries
Poland
Georgia
further
demonstrate
feasibility.
enable
broader
adoption,
harmonization
advancements
production,
delivery,
quality
will
essential.
Notably,
affordability
scalability
position
it
especially
valuable
solution
developing
regions
grappling
escalating
rates
antibiotic
resistance.
Pharmaceutics,
Год журнала:
2025,
Номер
17(4), С. 470 - 470
Опубликована: Апрель 3, 2025
Pulmonary
delivery
of
bioactives
has
shown
to
be
a
promising
route
for
the
treatment
respiratory
conditions,
however,
numerous
physiological
barriers,
such
as
mucociliary
clearance
and
immune
responses,
pose
significant
hurdles
efficacy.
These
barriers
specifically
affect
labile
mRNA,
peptides,
proteins,
probiotics,
which
are
susceptible
degradation
due
prevailing
conditions.
Various
drug
platforms
have
been
developed
address
these
challenges,
including,
among
others,
polymeric
nanoparticles,
micelles,
liposomes,
solid
lipid
nanoparticles
that
encapsulate
protect
during
formulation
administration,
enabling
improved
bioavailability,
sustained
release,
enhanced
stability,
while
further
modification
allows
targeted
delivery.
This
review
explores
advanced
systems
designed
release
active
agents
in
controlled
manner
lung,
with
specific
focus
provided
on
effective
pulmonary
considerations
overcome
challenges.
The
outlook
this
pertinent
field
study
additionally
provided,
highlighting
potential
bioactive
prevention
variety
ailments.
ABSTRACT
Streptococcus
pneumoniae
(
Sp
;
pneumococcus),
the
most
common
agent
of
community‐acquired
pneumonia,
can
spread
systemically,
particularly
in
elderly,
highlighting
need
for
adjunctive
therapies.
The
airway
epithelial
barrier
defends
against
bacteremia
and
is
dependent
upon
apical
junctional
complex
(AJC)
proteins
such
as
E‐cadherin.
After
mouse
lung
challenge,
pneumolysin
(PLY),
a
key
virulence
factor,
stimulates
secretion
an
inflammatory
eicosanoid,
triggering
infiltration
polymorphonuclear
leukocytes
(PMNs)
that
secrete
high
levels
neutrophil
elastase
(NE),
thus
promoting
damage
systemic
infection.
Here,
pulmonary
E‐cadherin
staining
intratracheally
i.t.
)
inoculated
mice
revealed
PLY‐mediated
disruption
AJC
independently
PMNs.
Apical
infection
air–liquid
interface
(ALI)
respiratory
monolayers
similarly
showed
PLY
disrupts
AJCs.
This
promoted
PMN
transmigration
bacterial
apical‐to‐basolateral
translocation,
pharmacologically
fortifying
function
diminished
both
breach
vitro
vivo.
after
inoculation
>
20‐month‐old
mice,
or
ALI
derived
from
these
age‐associated
vulnerability
to
disruption,
which
turn
enhanced
migration
bacteremia.
In
addition,
we
found
PMNs
aged
increased
tissue‐damaging
NE.
Simultaneous
pharmacological
inhibition
tissue‐destructive
NE
fortification
was
required
reduce
level
young
mice.
work
underscores
importance
fully
characterizing
multifactorial
sources
susceptibility
devising
therapies
mitigate
invasive
pneumococcal
disease
elderly.
Pharmaceuticals,
Год журнала:
2025,
Номер
18(2), С. 195 - 195
Опубликована: Янв. 31, 2025
Drugs
administered
by
means
of
extravascular
routes
drug
administration
must
be
absorbed
into
the
systemic
circulation,
which
involves
movement
molecules
across
biological
barriers
such
as
epithelial
cells
that
cover
mucosal
surfaces
or
stratum
corneum
covers
skin.
Some
drugs
exhibit
poor
permeation
membranes
may
experience
excessive
degradation
during
first-pass
metabolism,
tends
to
limit
their
bioavailability.
Various
strategies
have
been
used
improve
Absorption
enhancement
include
co-administration
chemical
enhancers,
enzymes,
and/or
efflux
transporter
inhibitors,
changes,
and
specialized
dosage
form
designs.
Models
with
physiological
relevance
are
needed
evaluate
efficacy
absorption
techniques.
in
vitro
cell
culture
models
ex
vivo
tissue
explored
quantify
effectiveness
strategies.
This
review
deliberates
on
use
for
evaluation
selected
including
nasal,
oromucosal,
pulmonary,
oral,
rectal,
transdermal
administration.
Journal of Inflammation Research,
Год журнала:
2025,
Номер
Volume 18, С. 1657 - 1678
Опубликована: Фев. 1, 2025
Background:
Associations
between
ulcerative
colitis
(UC)
and
ankylosing
spondylitis
(AS)
have
been
reported
in
multiple
studies,
but
the
common
etiologies
of
UC
AS
remain
unknown.
Thus,
current
study,
we
aimed
to
investigate
shared
genes
relevant
mechanisms
AS.
Methods:
Using
datasets
for
(GSE113079)
(GSE1797879),
initially
identified
differentially
expressed
(DEGs)
through
differential
expression
analysis.
The
DEGs
from
both
were
intersected
identify
DEGs,
AS,
which
used
receiver
operating
characteristic
(ROC)
curve
analysis
confirm
key
pathway.
Gene
set
enrichment
(GSEA)
was
obtain
information
on
gene
pathways
interactions
with
or
AS-related
diseases,
followed
by
immune
infiltration
Finally,
peripheral
blood
samples
verify
mRNA
eight
using
reverse
transcription-polymerase
chain
reaction
(RT-PCR).
Results:
Our
results
revealed
that
GMFG,
GNG11,
CLEC4D,
CMTM2,
VAMP5,
S100A8,
S100A12
DGKQ
are
potential
diagnostic
biomarkers
UC.
Rimegepant,
eptinezumab,
methotrexate,
atogepant,
ubrogepant
as
drugs
S100A8
patients
GSEA
showed
these
associated
antigen
processing
presentation,
natural
killer
cell
mediated
cytotoxicity
T
receptor
signaling
pathway
UC,
significantly
cells
various
immune-related
pathways.
Subsequent
functional
experiments
significant
increases
expressions
VAMP5
Additionally,
CLEC4D
notably
higher
than
healthy
controls.
Conclusion:
Key
may
improve
understanding
their
relationship
guide
diagnosis
treatment
strategies.
Keywords:
colitis,
spondylitis,
diagnosis,
etiology
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Фев. 21, 2025
Occupational
exposure
to
engineered
nanomaterials
(ENMs)
is
increasing
in
the
workplace
and
can
impact
human
health.
Amorphous
silicon
dioxide
nanoparticles
(SiO2
NPs)
are
widely
produced
respirable
ENMs
used
commercial
products.
We
have
investigated
their
on
lung
inflammation
resolution
bacterial
defense.
Mice
exposed
SiO2
NPs,
followed
by
bacteria,
exhibited
increased
inflammation,
proliferation,
damage
compared
mice
not
NPs.
NPs
macrophage
production
of
pro-inflammatory
mediators
disrupted
phagocytosis
bacteria
efferocytosis
apoptotic
neutrophils
–
pivotal
responses
for
host
defense
resolution.
A
pro-resolving
mediator,
resolvin
D5
(RvD5),
restored
partially
controlled
excess
after
These
findings
demonstrate
that
disrupt
endogenous
processes
give
rise
heightened
infection.
RvD5
reduced
cellular
processes,
suggesting
reduce
ENP
disruption
