Science Advances,
Journal Year:
2022,
Volume and Issue:
8(24)
Published: June 17, 2022
The
female
ovary
contains
a
finite
number
of
oocytes,
and
their
release
at
ovulation
becomes
sporadic
disordered
with
aging
obesity,
leading
to
loss
fertility.
Understanding
the
molecular
defects
underpinning
this
pathology
is
essential
as
age
childbearing
obesity
rates
increase
globally.
We
identify
that
fibrosis
within
ovarian
stromal
compartment
an
underlying
mechanism
responsible
for
impaired
oocyte
release,
which
initiated
by
mitochondrial
dysfunction
diminished
bioenergetics,
oxidative
damage,
inflammation,
collagen
deposition.
Furthermore,
antifibrosis
drugs
(pirfenidone
BGP-15)
eliminate
fibrotic
restore
in
reproductively
old
obese
mice,
association
dampened
M2
macrophage
polarization
up-regulated
MMP13
protease.
This
first
evidence
reversible
indicates
targeting
metabolism
may
be
viable
therapeutic
strategy
women
metabolic
disorders
or
advancing
maintain
function
extend
JAMA,
Journal Year:
2023,
Volume and Issue:
329(9), P. 725 - 725
Published: March 7, 2023
Importance
Olamkicept,
a
soluble
gp130-Fc-fusion-protein,
selectively
inhibits
interleukin
6
(IL-6)
trans-signaling
by
binding
the
IL-6
receptor/IL-6
complex.
It
has
anti-inflammatory
activities
in
inflammatory
murine
models
without
immune
suppression.
Objective
To
assess
effect
of
olamkicept
as
induction
therapy
patients
with
active
ulcerative
colitis.
Design,
Setting,
and
Participants
Randomized,
double-blind,
placebo-controlled
phase
2
trial
91
adults
colitis
(full
Mayo
score
≥5,
rectal
bleeding
≥1,
endoscopy
≥2)
an
inadequate
response
to
conventional
therapy.
The
study
was
conducted
at
22
clinical
sites
East
Asia.
Patients
were
recruited
beginning
February
2018.
Final
follow-up
occurred
December
2020.
Interventions
Eligible
randomized
1:1:1
receive
biweekly
intravenous
infusion
600
mg
(n
=
30)
or
300
31)
placebo
for
12
weeks.
Main
Outcomes
Measures
primary
end
point
week
(defined
≥3
≥30%
decrease
from
baseline
total
score;
range,
0-12
[worst]
≥1
≤1
[range,
0-3
{worst}]).
There
25
secondary
efficacy
outcomes,
including
remission
mucosal
healing
12.
Results
Ninety-one
(mean
age,
41
years;
women
[27.5%])
randomized;
79
(86.8%)
completed
trial.
At
12,
more
receiving
(17/29
[58.6%])
(13/30
[43.3%])
achieved
than
(10/29
[34.5%]),
adjusted
difference
vs
26.6%
(90%
CI,
6.2%
47.1%;
P
.03)
8.3%
−12.6%
29.1%;
.52)
mg.
Among
olamkicept,
16
outcomes
statistically
significant
compared
placebo.
mg,
Treatment-related
adverse
events
53.3%
(16/30)
58.1%
(18/31)
50%
(15/30)
most
common
drug-related
bilirubin
presence
urine,
hyperuricemia,
increased
aspartate
aminotransferase
levels,
all
groups
Conclusions
Relevance
colitis,
but
not
resulted
greater
likelihood
weeks
Further
research
is
needed
replication
longer-term
safety.
Trial
Registration
ClinicalTrials.gov
Identifier:
NCT03235752
Thorax,
Journal Year:
2023,
Volume and Issue:
78(8), P. 835 - 839
Published: May 19, 2023
Treatment
with
elexacaftor/tezacaftor/ivacaftor
(ETI)
has
been
shown
to
improve
lung
function
in
people
cystic
fibrosis
(PWCF).
However,
its
biological
effects
remain
incompletely
understood.
Here
we
describe
alterations
pulmonary
and
systemic
inflammation
PWCF
following
initiation
of
ETI.
To
address
this,
collected
spontaneously
expectorated
sputum
matching
plasma
from
(n=30)
immediately
prior
ETI
therapy,
then
again
at
3
12
months.
Within
months,
demonstrated
reduced
activity
neutrophil
elastase,
proteinase
three
cathepsin
G,
decreased
concentrations
interleukin
(IL)−1β
IL-8
sputum,
accompanied
by
Pseudomonas
burden
restoration
secretory
leukoprotease
inhibitor
levels.
Once
treated
ETI,
all
airway
inflammatory
markers
studied
had
levels
found
matched
non-CF
bronchiectasis
controls.
In
advanced
disease,
resulted
IL-6,
C-reactive
protein
soluble
TNF
receptor
one
as
well
normalisation
the
acute
phase
protein,
alpha-1
antitrypsin.
These
data
clarify
immunomodulatory
underscore
role
a
disease
modifier.
Sensors and Actuators B Chemical,
Journal Year:
2024,
Volume and Issue:
404, P. 135282 - 135282
Published: Jan. 5, 2024
Interleukin-6
(IL-6)
is
an
important
cytokine
involved
in
immune
responses
and
maintaining
body
homeostasis.
Elevated
IL-6
levels,
exceeding
~40
pg/mL
bodily
fluids,
are
associated
with
inflammation
diseases
such
as
COVID-19,
cardiovascular
disorders,
Alzheimer's,
necessitating
real-time
health
monitoring
for
personalized
healthcare.
In
this
study,
we
developed
a
highly
sensitive
selective
sensing
platform
by
depositing
poly(o-phenylenediamine)
(P(o-PD))-based
molecularly
imprinted
polymer
(MIP)
onto
oxygen-functionalized
screen-printed
carbon
electrode
gold
nanoparticles,
3-aminopropyltriethoxysilane
(APTES),
glutaraldehyde
(GA).
While
APTES
enhanced
the
peak
current
due
to
redox
probe
adsorption,
GA
reduced
it
non-conductive
aldehyde
groups.
This
functionalized
surface
improved
hydrophilicity
presence
of
amino
carbonyl
We
identified
that
120-minute
NaCl
treatment
effectively
removed
templates,
ensuring
successful
embedding
P(o-PD)
matrix.
calculated
imprinting
factor
11.2,
indicating
effective
specific
binding
sites
within
MIP,
resulting
robust
response
IL-6.
After
optimizing
MIP
deposition
through
five
cycles,
detected
concentrations
ranging
from
2
400
pg/mL,
sensitivity
3.48
μA/log(pg/mL)
limit
detection
1.74
pg/mL.
When
tested
real
human
serum,
sensor
encountered
challenges
matrix
adsorbing
other
active
molecules.
Despite
challenge,
our
demonstrates
high
selectivity
long-term
stability
detection.
These
qualities
position
well-suited
point-of-care
diagnostics,
emphasizing
its
potential
reliable
tool
real-world
applications.
American Journal of Hematology,
Journal Year:
2021,
Volume and Issue:
96(10), P. 1241 - 1252
Published: July 15, 2021
Thrombocytopenia,
anasarca,
fever,
reticulin
fibrosis,
renal
insufficiency,
and
organomegaly
(TAFRO)
syndrome
is
a
heterogeneous
entity
manifesting
with
constellation
of
symptoms
described
above
that
can
occur
in
the
context
idiopathic
multicentric
Castleman
disease
(iMCD)
as
well
infectious
diseases,
malignancies,
rheumatologic
disorders.
So,
iMCD-TAFRO
an
aggressive
subtype
iMCD
TAFRO
often
hyper-vascularized
lymph
nodes.
Since
we
proposed
diagnostic
criteria
2016,
have
accumulated
new
insights
on
disorder
additional
cases
been
reported
worldwide.
In
this
systematic
review
cohort
analysis,
established
validated
definition
for
iMCD-TAFRO.
First,
searched
PubMed
Japan
Medical
Abstracts
Society
databases
using
keyword
"TAFRO"
to
extract
cases.
Patients
possible
systemic
autoimmune
diseases
hematologic
malignancies
were
excluded.
Our
search
identified
54
from
50
articles.
We
classified
into
three
categories:
(1)
(TAFRO
node
histopathology
consistent
iMCD),
(2)
no
biopsy
performed
other
co-morbidities),
(3)
without
or
co-morbidities
not
comorbidities).
Based
findings,
propose
international
requiring
four
clinical
(thrombocytopenia,
fever/hyperinflammatory
status,
organomegaly),
dysfunction
characteristic
bone
marrow
features
iMCD.
The
was
external
(the
ACCELERATE
Natural
History
Registry).
present
will
facilitate
more
precise
comprehensive
approach
diagnosis
Diseases,
Journal Year:
2021,
Volume and Issue:
9(3), P. 47 - 47
Published: June 29, 2021
Coronavirus
disease
2019
(COVID-19)
has
been
reported
to
cause
cardiovascular
complications
such
as
myocardial
injury,
thromboembolic
events,
arrhythmia,
and
heart
failure.
Multiple
mechanisms—some
overlapping,
notably
the
role
of
inflammation
IL-6—potentially
underlie
these
complications.
The
cardiac
injury
may
be
a
result
direct
viral
invasion
cardiomyocytes
with
consequent
unopposed
effects
angiotensin
II,
increased
metabolic
demand,
immune
activation,
or
microvascular
dysfunction.
Thromboembolic
events
have
widely
in
both
venous
arterial
systems
that
attracted
intense
interest
underlying
mechanisms.
These
could
potentially
due
endothelial
dysfunction
secondary
inflammation.
Additionally,
also
consequence
an
attempt
by
system
contain
infection
through
immunothrombosis
neutrophil
extracellular
traps.
Cardiac
arrhythmias
wide
range
implicated
contributory
factors,
ranging
from
well
other
including
at-risk
individuals
inherited
arrhythmia
syndromes.
Heart
failure
occur
progression
precipitation
initiation
withdrawal
certain
drugs,
accumulation
des-Arg9-bradykinin
(DABK)
excessive
induction
pro-inflammatory
G
protein
coupled
receptor
B1
(BK1).
presenting
symptoms
include
chest
pain,
dyspnoea,
palpitations.
There
is
currently
vaccine-induced
thrombosis
treatment
Long
COVID
since
many
patients
who
survived
COVID-19
describe
persisting
health
problems.
This
review
will
summarise
proposed
physiological
mechanisms
COVID-19-associated
Brain,
Journal Year:
2022,
Volume and Issue:
145(10), P. 3444 - 3453
Published: June 3, 2022
Abstract
There
is
increasing
evidence
for
inflammation
as
a
determinant
in
the
pathogenesis
of
Parkinson’s
disease,
but
its
role
parkinsonian
neurodegeneration
remains
elusive.
It
not
clear
whether
inflammatory
cascades
are
causes
or
consequences
dopamine
neuron
death.
In
present
study,
we
aim
to
perform
an
in-depth
statistical
investigation
causal
relationship
between
and
disease
using
two-sample
Mendelian
randomization
design.
Genetic
instruments
were
selected
summary-level
data
from
largest
genome-wide
association
studies
date
(sample
size
ranging
13
955
204
402
individuals)
conducted
on
European
population
following
biomarkers:
C-reactive
protein,
interleukin-6,
interleukin
1
receptor
antagonist
tumour
necrosis
factor
α.
(56
306
cases
417
791
controls)
age
at
onset
(28
568
cases)
obtained
International
Disease
Genomics
Consortium.
On
primary
analysis,
associations
estimated
sets
strong
(P-value
<
5
×
10−8;
F-statistic
>
10)
independent
(linkage
disequilibrium
r2
0.001)
genetic
inverse-variance
weighted
method.
sensitivity
effects
robust
methods
after
removing
pleiotropic
variants.
Reverse
causation
was
also
explored.
We
repeated
analysis
different
sources
biomarkers
check
consistency
findings.
all
three
found
earlier
associated
with
increased
interleukin-6
concentration
[years
difference
per
log-unit
increase
=
−2.364,
95%
confidence
interval
(CI)
−4.789–0.060;
years
−2.011,
CI
−3.706
−0.317;
−1.569,
−2.891
−0.247].
did
observe
any
α
both
onset.
Results
excluding
possible
variants
consistent
findings
analyses.
When
investigating
reverse
causation,
find
effect
inflammation.
interleukin-6.
The
this
study
suggest
that
pro-inflammatory
activity
cytokine
could
be
prodromal
disease.
