Pharmaceutics,
Journal Year:
2021,
Volume and Issue:
13(10), P. 1585 - 1585
Published: Sept. 29, 2021
Adenoviruses
represent
exceptional
candidates
for
wide-ranging
therapeutic
applications,
from
vectors
gene
therapy
to
oncolytics
cancer
treatments.
The
first
ever
commercial
medicine
was
based
on
a
recombinant
adenovirus
vector,
while
most
recently,
adenoviral
have
proven
critical
as
vaccine
platforms
in
effectively
controlling
the
global
coronavirus
pandemic.
Here,
we
discuss
factors
involved
cell
binding,
entry,
and
trafficking;
how
they
influence
efficiency
of
adenovirus-based
vectors;
can
be
manipulated
enhance
efficacy
genetically
modified
variants.
We
focus
particularly
endocytosis
different
serotypes
employ
endocytic
pathways
gain
thus,
intracellular
trafficking
that
subsequently
trigger
host
antiviral
responses.
In
context
therapy,
final
goal
vector
is
efficiently
deliver
transgenes
into
target
nucleus,
thus
allowing
its
functional
expression.
Aberrant
or
inefficient
impede
this
goal,
therefore,
it
should
considered
when
designing
constructing
vectors.
Signal Transduction and Targeted Therapy,
Journal Year:
2022,
Volume and Issue:
7(1)
Published: Aug. 2, 2022
Abstract
Disturbed
cholesterol
homeostasis
plays
critical
roles
in
the
development
of
multiple
diseases,
such
as
cardiovascular
diseases
(CVD),
neurodegenerative
and
cancers,
particularly
CVD
which
accumulation
lipids
(mainly
cholesteryl
esters)
within
macrophage/foam
cells
underneath
endothelial
layer
drives
formation
atherosclerotic
lesions
eventually.
More
more
studies
have
shown
that
lowering
level,
especially
low-density
lipoprotein
protects
system
prevents
events
effectively.
Maintaining
is
determined
by
biosynthesis,
uptake,
efflux,
transport,
storage,
utilization,
and/or
excretion.
All
processes
should
be
precisely
controlled
regulatory
pathways.
Based
on
regulation
homeostasis,
many
interventions
been
developed
to
lower
inhibiting
biosynthesis
uptake
or
enhancing
utilization
Herein,
we
summarize
historical
review
research
events,
current
understandings
molecular
pathways
playing
key
regulating
cholesterol-lowering
clinics
preclinical
well
new
targets
their
clinical
advances.
importantly,
discuss
benefits
those
for
treatment
including
obesity,
diabetes,
nonalcoholic
fatty
liver
disease,
cancer,
osteoporosis
virus
infection.
Advanced Healthcare Materials,
Journal Year:
2023,
Volume and Issue:
12(25)
Published: June 29, 2023
Abstract
A
key
aspect
for
successful
drug
delivery
via
lipid‐based
nanoparticles
is
their
internalization
in
target
cells.
Two
prominent
examples
of
such
systems
are
artificial
phospholipid‐based
carriers,
as
liposomes,
and
biological
counterparts,
the
extracellular
vesicles
(EVs).
Despite
a
wealth
literature,
it
remains
unclear
which
mechanisms
precisely
orchestrate
nanoparticle‐mediated
cargo
to
recipient
cells
subsequent
intracellular
fate
therapeutic
cargo.
In
this
review,
involved
uptake
liposomes
EVs
by
evaluated,
also
exploring
after
trafficking.
Opportunities
highlighted
tweak
these
fates
enhance
efficacy
systems.
Overall,
literature
date
shows
that
both
predominantly
internalized
through
classical
endocytosis
mechanisms,
sharing
common
fate:
accumulation
inside
lysosomes.
Studies
tackling
differences
between
EVs,
with
respect
cellular
uptake,
therapy
efficacy,
remain
scarce,
despite
its
importance
selection
an
appropriate
system.
addition,
further
exploration
functionalization
strategies
represents
important
avenue
pursue
order
control
fate,
thereby
improving
efficacy.
Frontiers in Immunology,
Journal Year:
2021,
Volume and Issue:
12
Published: Dec. 16, 2021
Since
its
appearance,
the
Severe
Acute
Respiratory
Syndrome
Coronavirus
(SARS-CoV-2),
causal
agent
of
Disease
2019
(COVID-19),
represents
a
global
problem
for
human
health
that
involves
host
lipid
homeostasis.
Regarding,
rafts
are
functional
membrane
microdomains
with
highly
and
tightly
packed
molecules.
These
regions
enriched
in
sphingolipids
cholesterol
recruit
concentrate
several
receptors
molecules
involved
pathogen
recognition
cellular
signaling.
Cholesterol-rich
have
multiple
functions
viral
replication;
however,
their
role
SARS-CoV-2
infection
remains
unclear.
In
this
review,
we
discussed
novel
evidence
on
cholesterol-rich
as
platform
entry,
where
such
angiotensin-converting
enzyme-2
(ACE-2),
heparan
sulfate
proteoglycans
(HSPGs),
Toll-like
(TLRs),
transmembrane
serine
proteases
(TMPRSS),
CD-147
HDL-scavenger
receptor
B
type
1
(SR-B1)
recruited
interaction
spike
protein.
FDA-approved
drugs
statins,
metformin,
hydroxychloroquine,
cyclodextrins
(methyl-β-cyclodextrin)
can
disrupt
to
regulate
key
immune
signaling
pathways
triggered
by
infection.
Taken
together,
better
knowledge
SARS-CoV-2-host
interactions
will
provide
valuable
insights
into
pathogenesis
identification
therapeutic
targets.
Cell Communication and Signaling,
Journal Year:
2023,
Volume and Issue:
21(1)
Published: Jan. 23, 2023
Abstract
As
a
common
belief,
most
viruses
can
egress
from
the
host
cells
as
single
particles
and
transmit
to
uninfected
cells.
Emerging
data
have
revealed
en
bloc
viral
transmission
lipid
bilayer-cloaked
via
extracellular
vesicles
especially
exosomes
(Exo).
The
supporting
membrane
be
originated
multivesicular
bodies
during
intra-luminal
vesicle
formation
autophagic
response.
Exo
are
nano-sized
particles,
ranging
40–200
nm,
with
ability
harbor
several
types
of
signaling
molecules
donor
acceptor
in
paracrine
manner,
resulting
modulation
specific
reactions
target
phenomenon
biogenesis
consists
multiple
complex
biological
steps
participation
diverse
constituents
molecular
pathways.
Due
similarities
between
virus
replication
existence
shared
pathways,
it
is
thought
that
hijack
machinery
spread
evade
immune
To
this
end,
complete
virions
(as
units
or
aggregates),
separate
components,
naked
genetic
materials.
current
review
article
aims
scrutinize
challenges
opportunities
related
exosomal
delivery
terms
infections
public
health.
Biomedicines,
Journal Year:
2024,
Volume and Issue:
12(7), P. 1523 - 1523
Published: July 9, 2024
The
Central
Nervous
System
(CNS)
is
vulnerable
to
a
range
of
diseases,
including
neurodegenerative
and
oncological
conditions,
which
present
significant
treatment
challenges.
blood–brain
barrier
(BBB)
restricts
molecule
penetration,
complicating
the
achievement
therapeutic
concentrations
in
CNS
following
systemic
administration.
Gene
therapy
using
recombinant
adeno-associated
virus
(rAAV)
vectors
emerges
as
promising
strategy
for
treating
demonstrated
by
registration
six
gene
products
past
years
87
ongoing
clinical
trials.
This
review
explores
implementation
rAAV
disease
treatment,
emphasizing
AAV
biology
vector
engineering.
Various
administration
methods—such
intravenous,
intrathecal,
intraparenchymal
routes—and
experimental
approaches
like
intranasal
intramuscular
are
evaluated,
discussing
their
advantages
limitations
different
contexts.
Additionally,
underscores
importance
optimizing
efficacy
through
pharmacokinetics
(PK)
pharmacodynamics
(PD)
vectors.
A
comprehensive
analysis
trials
reveals
successes
challenges,
barriers
commercialization.
provides
insights
into
strategies
neurological
diseases
identifies
areas
requiring
further
research,
particularly
PK/PD.
Life Science Alliance,
Journal Year:
2024,
Volume and Issue:
7(5), P. e202302453 - e202302453
Published: Feb. 22, 2024
The
rapid
development
of
vaccines
to
combat
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
infections
has
been
critical
reduce
the
severity
COVID-19.
However,
continuous
emergence
new
SARS-CoV-2
subtypes
highlights
need
develop
additional
approaches
that
oppose
viral
infections.
Targeting
host
factors
support
virus
entry,
replication,
and
propagation
provide
opportunities
lower
infection
rates
improve
COVID-19
outcome.
This
includes
cellular
cholesterol,
which
is
for
spike
proteins
capture
machinery
cell
entry.
Once
endocytosed,
exit
from
late
endosomal/lysosomal
compartment
occurs
in
a
cholesterol-sensitive
manner.
In
addition,
effective
release
particles
also
requires
cholesterol.
Hence,
cholesterol-lowering
statins,
proprotein
convertase
subtilisin/kexin
type
9
antibodies,
ezetimibe
have
revealed
potential
protect
against
pharmacological
inhibition
cholesterol
exiting
endosomes/lysosomes
identified
drug
candidates,
including
antifungals,
block
infection.
review
describes
multiple
roles
at
surface
endolysosomes
entry
drugs
targeting
homeostasis
infectivity
disease
severity.
Frontiers in Cell and Developmental Biology,
Journal Year:
2021,
Volume and Issue:
9
Published: June 17, 2021
Severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
is
the
cause
of
COVID-19
pandemic
with
severe
consequences
for
afflicted
individuals
and
society
as
a
whole.
The
biology
infectivity
virus
has
been
intensively
studied
in
order
to
gain
better
understanding
molecular
basis
virus-host
cell
interactions
during
infection.
It
known
that
SARS-CoV-2
binds
angiotensin-converting
enzyme
(ACE2)
via
its
spike
protein.
Priming
by
specific
proteases
leads
viral
entry
endocytosis
subsequent
steps
life
cycle
SARS-CoV-2.
Sphingosine
ceramide
belong
sphingolipid
family
are
abundantly
present
membranes.
These
lipids
were
recently
shown
interfere
uptake
particles
into
epithelial
lines
primary
human
nasal
cells
culture.
mechanisms
action
partly
different,
sphingosine
blocked,
whilst
facilitated
entry.
Acid
sphingomyelinase
(ASM)
vital
generation
functional
inhibition
ASM
drugs
like
amitriptyline
reduced
cells.
Recent
data
indicates
serum
level
sphingosine-1-phosphate
(S1P)
prognostic
factor
COVID-2
severity.
Further,
stimulation
receptor
1
(S1PR1)
might
also
constrain
hyper-inflammatory
conditions
linked
Here,
we
review
recent
exciting
findings
regarding
sphingolipids
course
disease.
More
studies
required
on
potential
use
antidepressant
modifiers
infections
treatment
more
serious
fatal
