Chemical Biology & Drug Design,
Год журнала:
2024,
Номер
104(6)
Опубликована: Дек. 1, 2024
ABSTRACT
The
immune
system
is
essential
for
the
defense
against
infections
and
critically
implicated
in
various
disorders,
including
immunodeficiency,
autoimmunity,
inflammation
cancer.
current
study
includes
a
new
design
of
palmitoylated
derivatives
thioglycolic
acids
(PTGAs)
capable
triggering
innate
responses.
series
were
accessible
through
three‐step
synthetic
route,
N
‐palmitoylation,
Claisen–Schmidt
condensation
thia‐Michael
addition.
Their
structures
elucidated
using
different
1D
2D
NMR
spectroscopic
techniques
their
purity
was
confirmed
by
elemental
analysis.
most
active
PTGAs
induced
12–26‐fold
increase
expression
TNF‐α
IL‐1β
mRNA
triggered
marked
release
NO
isolated
macrophages.
These
levels
comparable
to
responses
elicited
heat‐killed
E.
coli
S.
aureus
.
position
palmitamide
chain
aryl
substitution
had
significant
effect
on
release.
Simulations
molecular
dockings
showed
that
PTGA
occupy
same
TLR2/TLR6
heterodimer
binding
site
microbial
diacylated
lipoproteins.
immunomodulators
may
have
profound
impact
clinical
disorders
associated
with
dysfunctional
immunity.
The
innate
immune
system
serves
as
the
body's
first
line
of
defense,
utilizing
pattern
recognition
receptors
like
Toll-like
to
detect
pathogens
and
initiate
rapid
response
mechanisms.
Following
this
initial
response,
adaptive
immunity
provides
highly
specific
sustained
killing
via
B
cells,
T
antibodies.
Traditionally,
it
has
been
assumed
that
activates
immunity;
however,
recent
studies
have
revealed
more
complex
interactions.
This
review
a
detailed
dissection
composition
function
systems,
emphasizing
their
synergistic
roles
in
physiological
pathological
contexts,
providing
new
insights
into
link
between
these
two
forms
immunity.
Precise
regulation
both
systems
at
same
time
is
beneficial
fight
against
immune-related
diseases,
for
example,
cGAS-STING
pathway
found
play
an
important
role
infections
cancers.
In
addition,
paper
summarizes
challenges
future
directions
field
immunity,
including
latest
single-cell
sequencing
technologies,
CAR-T
cell
therapy,
checkpoint
inhibitors.
By
summarizing
developments,
aims
enhance
our
understanding
complexity
interactions
perspectives
system.
medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 5, 2025
Abstract
Motivation
The
analysis
of
complex
biomedical
datasets
is
becoming
central
to
understanding
disease
mechanisms,
aiding
risk
stratification
and
guiding
patient
management.
However,
the
utility
computational
methods
often
constrained
by
their
lack
interpretability
accessibility
for
non-experts,
which
particularly
relevant
in
clinically
critical
areas
where
rapid
initiation
targeted
therapies
key.
Results
To
define
diagnostically
immune
signatures
peritoneal
dialysis
patients
presenting
with
acute
peritonitis,
we
analysed
a
comprehensive
array
cellular
soluble
parameters
cloudy
effluents.
Utilising
Tsetlin
Machines
(TMs),
logic-based
machine
learning
approach,
identified
pathogen-specific
fingerprints
different
bacterial
groups,
each
characterised
unique
biomarker
combinations.
Unlike
traditional
‘black
box’
models
such
as
artificial
neural
networks,
TMs
clear,
logical
rules
dataset
that
pointed
towards
distinctly
nuanced
responses
types
infection.
This
demonstrates
unambiguously
even
when
infecting
same
anatomical
location
causing
indistinguishable
symptoms,
type
pathogens
interacts
specific
way
body’s
system.
Importantly,
these
could
be
easily
visualised
facilitate
interpretation,
thereby
not
only
enhancing
diagnostic
accuracy
but
also
potentially
allowing
rapid,
accurate
transparent
decision-making
based
on
patient’s
profile.
capacity
help
deliver
clear
actionable
insights
early
support
informed
treatment
choices
advance
conventional
microbiological
culture
results,
thus
antibiotic
stewardship
contributing
improved
outcomes.
Availability
implementation
All
underlying
tools
present
are
available
at
https://github.com/anatoliy-gorbenko/biomarkers-visualization
.
anonymised
data
this
article
will
shared
reasonable
request
corresponding
authors.
Biomolecules,
Год журнала:
2025,
Номер
15(4), С. 487 - 487
Опубликована: Март 26, 2025
Immunity
is
a
fundamental
aspect
of
animal
biology,
defined
as
the
host’s
ability
to
detect
and
defend
against
harmful
pathogens
toxic
substances
preserve
homeostasis.
However,
immune
defenses
are
metabolically
demanding,
requiring
efficient
allocation
limited
resources
balance
function
with
other
physiological
developmental
needs.
To
achieve
this
balance,
organisms
have
evolved
sophisticated
signaling
networks
that
enable
precise,
context-specific
responses
internal
external
cues.
These
essential
for
survival
adaptation
in
multicellular
systems.
Central
regulatory
architecture
STAT
(signal
transducer
activator
Transcription)
family,
group
versatile
molecules
govern
wide
array
biological
processes
across
eukaryotes.
demonstrates
remarkable
plasticity,
from
orchestrating
host
defense
mechanisms
regulating
dietary
metabolism.
Despite
its
critical
role,
cell-specific
context-dependent
nuances
remain
incompletely
understood,
highlighting
significant
gap
our
understanding.
This
review
delves
into
emerging
perspectives
on
immunity,
presenting
dynamic
frameworks
explore
complexity
adaptability
underlying
logic
driving
cellular
decision-making.
It
emphasizes
how
pathways
integrate
diverse
processes,
regulation,
ultimately
supporting
organismal
PD-1/PD-L1
blockade
therapies
have
displayed
extraordinary
clinical
efficacy
for
melanoma,
renal,
bladder
and
lung
cancer;
however,
only
a
minority
of
colorectal
cancer
(CRC)
patients
benefit
from
these
treatments.
The
in
CRC
is
limited
by
the
complexities
tumor
microenvironment.
immunotherapy
based
on
T
cell-centered
view
immunity.
However,
onset
maintenance
cell
responses
development
long-lasting
memory
cells
depend
innate
immune
responses.
Acknowledging
pivotal
role
immunity
anti-tumor
response,
this
review
encapsulates
employment
combinational
those
involve
alongside
activation
explores
underlying
cellular
mechanisms,
aiming
to
harnessing
induce
control
who
received
therapy.
