BioFactors,
Journal Year:
2024,
Volume and Issue:
50(5), P. 997 - 1008
Published: March 23, 2024
Abstract
A
physiological
mechanism
of
programmed
cell
death
called
eryptosis
occurs
in
aged
or
damaged
red
blood
cells
(RBCs).
Dysregulated
contributes
to
abnormal
microcirculation
and
prothrombotic
risk.
Cigarette
smoke
extract
(CSE)
induces
a
p38
MAPK‐initiated,
Fas‐mediated
eryptosis,
activating
the
death‐inducing
signaling
complex
(DISC).
Indicaxanthin
(Ind)
from
cactus
pear
fruits,
is
bioavailable
dietary
phytochemical
humans
it
able
incorporate
into
RBCs
enhancing
their
defense
against
numerous
stimuli.
This
vitro
work
shows
that
Ind,
at
concentrations
mimic
plasma
after
fruit
meal,
protects
erythrocytes
CSE‐induced
eryptosis.
CSE
commercial
cigarettes
was
prepared
aqueous
solution
using
an
impinger
air
sampler
nicotine
content
determined.
were
treated
with
for
3
h
absence
presence
increasing
Ind
(from
1
5
μM).
Cytofluorimetric
measurements
indicated
reduced
phosphatidylserine
externalization
ceramide
formation
concentration‐dependent
manner.
Confocal
microscopy
visualization
coimmunoprecipitation
experiments
revealed
prevented
both
CSE‐triggered
Fas
aggregation
FasL/FADD/caspase
8
recruitment
membrane,
indicating
inhibition
DISC
assembly.
inhibited
phosphorylation
MAPK,
caspase‐8/caspase‐3
cleavage,
caspase‐3
activity
induced
by
CSE.
Finally,
ATP
depletion
restored
aminophospholipid
translocase
impaired
treatment.
In
conclusion,
comparable
nutritionally
relevant
concentrations,
can
prevent
RBC
CSE,
which
suggests
intake
fruits
may
limit
deleterious
effects
cigarette
smoking.
Molecular Biomedicine,
Journal Year:
2023,
Volume and Issue:
4(1)
Published: Nov. 8, 2023
Abstract
The
Janus
kinase-signal
transducer
and
transcription
activator
pathway
(JAK-STAT)
serves
as
a
cornerstone
in
cellular
signaling,
regulating
physiological
pathological
processes
such
inflammation
stress.
Dysregulation
this
can
lead
to
severe
immunodeficiencies
malignancies,
its
role
extends
neurotransduction
pro-inflammatory
signaling
mechanisms.
Although
JAK
inhibitors
(Jakinibs)
have
successfully
treated
immunological
inflammatory
disorders,
their
application
has
generally
been
limited
diseases
with
similar
pathogenic
features.
Despite
the
modest
expression
of
JAK-STAT
CNS,
it
is
crucial
for
functions
cortex,
hippocampus,
cerebellum,
making
relevant
conditions
like
Parkinson's
disease
other
neuroinflammatory
disorders.
Furthermore,
influence
on
serotonin
receptors
phospholipase
C
implications
stress
mood
This
review
expands
understanding
JAK-STAT,
moving
beyond
traditional
contexts
explore
stress-related
disorders
CNS
function.
Recent
findings,
effectiveness
Jakinibs
chronic
rheumatoid
arthritis,
expand
therapeutic
applicability.
Advances
isoform-specific
inhibitors,
including
filgotinib
upadacitinib,
promise
greater
specificity
fewer
off-target
effects.
Combination
therapies,
involving
monoclonal
antibodies,
aiming
enhance
efficacy
also
give
great
hope.
Overall,
bridges
gap
between
basic
science
clinical
application,
elucidating
complex
human
health
guiding
future
interventions.
Graphical
Pathophysiology,
Journal Year:
2023,
Volume and Issue:
30(3), P. 327 - 345
Published: Aug. 2, 2023
Diabetes
Mellitus
(DM)
is
a
complex
metabolic
disorder
associated
with
multiple
microvascular
complications
leading
to
nephropathy,
retinopathy,
and
neuropathy.
Mounting
evidence
suggests
that
red
blood
cell
(RBC)
alterations
are
both
cause
consequence
of
disturbances
related
DM-associated
complications.
Importantly,
significant
proportion
DM
patients
develop
varying
degrees
anemia
confounding
etiology,
increased
morbidity.
In
chronic
hyperglycemia,
RBCs
display
morphological,
enzymatic,
biophysical
changes,
which
in
turn
prime
them
for
swift
phagocytic
clearance
from
circulation.
A
multitude
endogenous
factors,
such
as
oxidative
dicarbonyl
stress,
uremic
toxins,
extracellular
hypertonicity,
sorbitol
accumulation,
deranged
nitric
oxide
metabolism,
have
been
implicated
pathological
RBC
changes
DM.
This
review
collates
clinical
laboratory
findings
hematology
indices
discusses
recent
reports
on
the
putative
mechanisms
underpinning
shortened
survival
disturbed
membrane
architecture
within
diabetic
milieu.
Specifically,
death
signaling,
procoagulant
phenotype,
RBC-triggered
endothelial
dysfunction,
deformability
aggregation
context
discussed.
Understanding
provides
valuable
insights
into
significance
crosstalk
between
microangiopathy
APOPTOSIS,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 9, 2025
Abstract
Over
the
recent
years,
our
understanding
of
cell
death
machinery
mature
erythrocytes
has
been
greatly
expanded.
It
resulted
in
discovery
several
regulated
(RCD)
pathways
red
blood
cells.
Apoptosis
(eryptosis)
and
necroptosis
share
certain
features
with
their
counterparts
nucleated
cells,
but
they
are
also
critically
different
particular
details.
In
this
review
article,
we
summarize
subroutines
erythroid
precursors
(apoptosis,
necroptosis,
ferroptosis)
comparison
to
(eryptosis
erythronecroptosis)
highlight
consequences
organelle
clearance
associated
loss
multiple
components
upon
erythrocyte
maturation.
Recent
advances
role
RCDs
health
disease
have
expanded
potential
clinical
applications
these
lethal
subroutines,
emphasizing
contribution
development
anemia,
microthrombosis,
endothelial
dysfunction,
as
well
diagnostic
biomarkers
markers
storage-induced
lesions.
Fas
signaling
functional
caspase-8/caspase-3
system
not
indispensable
for
eryptosis,
might
be
retained
mediate
crosstalk
between
both
erythrocyte-associated
RCDs.
The
ability
switch
eryptosis
suggests
that
is
a
simple
unregulated
mechanical
disintegration,
tightly
controlled
process.
This
allows
investigation
eventual
pharmacological
interventions
aimed
at
individual
erythrocytes.
Frontiers in Bioscience-Landmark,
Journal Year:
2024,
Volume and Issue:
29(10)
Published: Sept. 26, 2024
Since
2000s,
we
have
outlined
the
multifaceted
role
of
inflammation
in
several
aspects
cancer,
via
specific
inflammatory
mediators,
including
platelet
activating
factor
(PAF)
and
PAF-receptor
(PAFR)
related
signaling,
which
affect
important
junctions
cellular
interactions
that
are
associated
with
tumor-related
manifestations.
It
is
now
well
established
disease-related
unresolved
chronic
responses
can
promote
carcinogenesis.
At
same
time,
tumors
themselves
able
to
their
progression
metastasis,
by
triggering
an
inflammation-related
vicious
cycle,
PAF
its
signaling
play
crucial
role(s),
usually
conclude
tumor
growth
angiogenesis.
In
parallel,
new
evidence
suggests
also
interact
cancer
treatments
inducing
antitumor
immune
response
or,
conversely,
promoting
recurrence.
Within
this
review
article,
current
knowledge
future
perspectives
implication
all
these
thoroughly
re-assessed.
The
potential
beneficial
PAF-inhibitors
natural
or
synthetic
modulators
PAF-metabolism
against
tumors,
metastasis
evaluated.
Emphasis
given
molecules
dual
anti-PAF
anti-cancer
activities
(Bio-DAPAC-tives),
proven
potency
through
clinical
trials,
as
on
metal-based
anti-inflammatory
mediators
constitute
a
class
potent
inhibitors.
way
compounds
may
anti-tumor
effects
modulate
actions
discussed.
Limitations
targeting
PAF,
metabolism
receptor,
PAF-related
part(s)
strategies
involve
response(s)
for
improved
outcome,
Journal of Clinical Medicine,
Journal Year:
2024,
Volume and Issue:
13(7), P. 2049 - 2049
Published: April 2, 2024
Anemia
is
a
common
hematological
disorder
that
affects
12%
of
the
community-dwelling
population,
40%
hospitalized
patients,
and
47%
nursing
home
residents.
Our
understanding
impact
inflammation
on
iron
metabolism
erythropoiesis
still
lacking.
In
older
adults,
anemia
can
be
divided
into
nutritional
deficiency
anemia,
bleeding
unexplained
anemia.
The
last
type
might
caused
by
reduced
erythropoietin
(EPO)
activity,
progressive
EPO
resistance
bone
marrow
erythroid
progenitors,
chronic
subclinical
pro-inflammatory
state.
Overall,
one-third
patients
with
demonstrate
deficiency,
have
state
kidney
disease,
suffer
from
unknown
etiology.
Understanding
anemia’s
pathophysiology
in
people
aged
65
over
crucial
because
it
contributes
to
frailty,
falls,
cognitive
decline,
decreased
functional
ability,
higher
mortality
risk.
Inflammation
produces
adverse
effects
cells
system.
These
include
(hypoferremia),
production,
elevated
phagocytosis
erythrocytes
hepatic
splenic
macrophages.
Additionally,
causes
enhanced
eryptosis
due
oxidative
stress
circulation.
Identifying
mechanisms
behind
age-related
essential
for
better
preventing
adults.