Abstract
Aberrant
protein
secretion
is
a
central
driver
of
tissue
inflammation
and
destruction
in
rheumatoid
arthritis
(RA).
While
RA
fibroblast-like
synoviocytes
(FLSs)
exhibit
prominent
endoplasmic
reticulum
(ER)
Golgi,
the
mechanism
underlying
their
excessive
not
fully
understood.
Here,
we
identified
deficiency
de
novo
NAD
+
synthesis
enzyme,
quinolinate
phosphoribosyltransferase
(QPRT),
as
significant
abnormality
synovium.
QPRT
loss
counterintuitively
inflates
trans-Golgi
network
(TGN)
while
decreasing
cytoplasm,
ER
cis/medial-Golgi.
knockdown
promoted
Golgi
membrane
expansion
epithelial-to-mesenchymal-transition
(EMT)-associated
secretome
production
FLSs
by
suppressing
TGN-residing
PARP12,
resulting
mTORC1-mediated
translation
expansion.
Furthermore,
gene
therapy
restored
balance,
corrected
dysfunction,
reduced
cytokine
production,
improved
severity
mouse
models.
These
findings
underscore
QPRT’s
role
coordinating
regulatory
dynamics
compartmentalized
,
proposing
targeting
therapeutic
strategy
for
inflammatory,
secretory
Golgi-related
diseases.
The
epidemic
of
metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD)
is
increasingly
growing
worldwide.
Thus,
there
an
urgent
need
for
novel,
non-invasive,
and
reliable
biomarkers
to
replace
biopsy
the
diagnosis
prognosis
MASLD.
Circulating
peripheral
blood
mononuclear
cells
(PBMCs)
are
highly
responsive
various
stimuli
physiological
changes.
Beyond
their
immunomodulatory
role,
PBMC
may
act
as
sensors
in
several
cardiometabolic
disorders,
including
MASLD,
with
programs
shifting
accordingly.
Recent
evidence
suggests
a
link
between
impaired
mitochondrial
bioenergetics
Additionally,
respiration
intricately
linked
intracellular
depletion
oxidized
form
nicotinamide
adenine
dinucleotide
(NAD+)
cell
types.
Accumulating
preclinical
clinical
data
show
that
NAD+-increasing
strategies
protect
against
MASLD
by
restoring
NAD+
pools
improving
performance.
This
review
will
focus
on
[i]
relevance
dysfunction,
bioenergetics,
marker
[ii]
potential
benefits
precursors
MAFLD
relationship
improved
immune
cells.
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(24), P. 17198 - 17198
Published: Dec. 6, 2023
The
current
understanding
of
long
COVID
(LC)
is
still
limited.
This
review
highlights
key
findings
regarding
the
role
gut
microbiota,
mitochondria,
and
main
pathophysiological
aspects
LC
revealed
by
clinical
studies,
related
to
complex
interplay
between
infection,
intestinal
dysbiosis,
dysfunctional
systemic
inflammation
generated
in
a
vicious
circle,
reflecting
molecular
cellular
processes
from
"leaky
gut"
electron
transport
chain
(ETC)"
into
quantum
leap.
heterogeneity
has
hindered
progress
deciphering
all
mechanisms,
therefore,
approach
must
be
multidisciplinary,
with
special
focus
not
only
on
symptomatic
management
but
also
addressing
underlying
health
problems
patients.
It
imperative
further
assess
validate
effects
COVID-19
microbiome
their
relationship
infections
other
viral
agents
or
pathogens.
Further
studies
are
needed
better
understand
expand
interdisciplinary
points
view
that
required
accurately
diagnose
effectively
treat
this
heterogeneous
condition.
Given
ability
SARS-CoV-2
induce
autoimmunity
susceptible
patients,
they
should
monitored
for
symptoms
autoimmune
disease
after
contracting
infection.
One
question
remains
open,
namely,
whether
various
vaccines
developed
end
pandemic
will
autoimmunity.
Recent
data
highlighted
have
persistence
mitochondria
organs
such
as
heart
and,
lesser
extent,
kidneys,
liver,
lymph
nodes,
organism
been
able
clear
virus
lungs,
could
an
explanation
LC.
Cancers,
Journal Year:
2024,
Volume and Issue:
16(2), P. 309 - 309
Published: Jan. 11, 2024
Poor
survival
rates
of
squamous
cell
carcinomas
(SCCs)
are
associated
with
high
recurrence,
metastasis,
and
late
diagnosis,
due
in
part
to
a
limited
number
reliable
biomarkers.
Thus,
the
identification
signatures
improving
diagnosis
different
SCC
types
is
mandatory.
Considering
relevant
role
NAD+
metabolism
chemoprevention
therapy,
study
aimed
at
identifying
new
biomarkers
based
on
metabolism-related
gene
(NMRG)
expression.
Gene
expression
18
NMRGs
clinical-pathological
information
for
patients
head
neck
(HNSCC),
lung
(LuSCC),
cervix
(CeSCC)
from
The
Cancer
Genome
Atlas
(TCGA)
were
analyzed
by
several
bioinformatic
tools.
We
identified
16-NMRG
profile
discriminating
3
SCCs
non-correlated
tumors.
found
genes
HNSCC,
LuSCC,
CeSCC
diagnostic
power.
Notably,
three
SCC-type
specific
Furthermore,
displayed
power
characteristics.
Analyzing
tumor-infiltrating
immune
profiles
PD-1/PD-L1
levels,
we
that
NMRG
was
suppressive
microenvironment
mainly
HNSCC.
Finally,
evaluation
patient
potential
prognostic
Therefore,
our
analyses
indicate
as
an
important
source
therapeutic
targets.
Frontiers in Immunology,
Journal Year:
2024,
Volume and Issue:
15
Published: Feb. 14, 2024
Citation:
Dongoran
RA,
Mardiana
M,
Huang
C-Y
and
Situmorang
JH
(2024)
Boosting
NAD+
levels
through
fasting
to
aid
in
COVID-19
recovery.
Front.
Immunol.
15:1319106.
doi:
10.3389/fimmu.2024.1319106
Abstract
Aberrant
protein
secretion
is
a
central
driver
of
tissue
inflammation
and
destruction
in
rheumatoid
arthritis
(RA).
While
RA
fibroblast-like
synoviocytes
(FLSs)
exhibit
prominent
endoplasmic
reticulum
(ER)
Golgi,
the
mechanism
underlying
their
excessive
not
fully
understood.
Here,
we
identified
deficiency
de
novo
NAD
+
synthesis
enzyme,
quinolinate
phosphoribosyltransferase
(QPRT),
as
significant
abnormality
synovium.
QPRT
loss
counterintuitively
inflates
trans-Golgi
network
(TGN)
while
decreasing
cytoplasm,
ER
cis/medial-Golgi.
knockdown
promoted
Golgi
membrane
expansion
epithelial-to-mesenchymal-transition
(EMT)-associated
secretome
production
FLSs
by
suppressing
TGN-residing
PARP12,
resulting
mTORC1-mediated
translation
expansion.
Furthermore,
gene
therapy
restored
balance,
corrected
dysfunction,
reduced
cytokine
production,
improved
severity
mouse
models.
These
findings
underscore
QPRT’s
role
coordinating
regulatory
dynamics
compartmentalized
,
proposing
targeting
therapeutic
strategy
for
inflammatory,
secretory
Golgi-related
diseases.
