Pharmacophore,
Journal Year:
2023,
Volume and Issue:
14(6), P. 52 - 58
Published: Jan. 1, 2023
This
study
looked
at
a
few
confirmed
cases
of
chronic
lymphocytic
leukemia
(CLL)
that
may
have
had
mutations
in
the
human
B
lymphocyte
genome's
P-53
gene.The
ELISA
technique
was
used
to
determine
frequency
p-53
protein
expression
twenty
CLL
patients
undergoing
evaluation
stages
II-III
/
IV.In
17
20
cases,
average
amounts
proteins
were
found
be
16.76
μg/dl,
with
probability
index
p
=
0.034
and
CV
0.5%.It
discovered
as
illness
progressed,
proportion
positive
isoform
rose
above
normal.The
percentage
15%
±
2
1-2
100%
3-4.Recent
studies
shown
inhibits
kinase
B,
AMPK
protein,
mTOR
complex,
hence
mediating
genes
trigger
autophagy
stimulating
autophagy.One
potential
use
protein's
role
cancer
cell
is
development
novel
anti-cancer
medicinal
approach.When
patient
develops
resistance
initial
line
treatment,
approach
has
an
invaluable
prognostic
tool
for
CLL,
enabling
administration
customized
medication.
PLoS ONE,
Journal Year:
2024,
Volume and Issue:
19(9), P. e0310524 - e0310524
Published: Sept. 19, 2024
Background
Alpha-1
antitrypsin
deficiency
(AATD)
is
an
inherited
disease,
the
common
variant
caused
by
a
Pi*Z
mutation
in
SERPINA1
gene.
AAT
increases
risk
of
pulmonary
emphysema
and
liver
disease.
Berberine
(BBR)
nature
dietary
supplement
herbal
remedy.
Emerging
evidence
revealed
that
BBR
has
remarkable
liver-protective
properties
against
various
diseases.
In
present
study,
we
investigated
therapeutic
effects
toxicities
hepatocytes
transgenic
mice.
Methods
Huh7.5
Huh7.5Z
(which
carries
mutation)
cells
were
treated
with
different
concentrations
for
48
hours.
MTT
was
performed
cell
viability
assay.
Intracellular
levels
evaluated
western
blot.
vivo
studies
carried
out
wild
type,
native
phenotype
(Pi*M),
Mice
50
mg/kg/day
or
solvent
only
oral
administration
30
days.
Western
blot
histopathological
examinations
to
evaluate
benefits
toxicity
BBR.
Results
reduced
intracellular
cells,
meanwhile,
no
Pi*Z-specific
observed.
However,
did
not
reduce
load
but
significantly
potentiated
inflammation
fibrosis
accompanying
activation
unfolded
protein
response
mTOR
mice,
type
Pi*M
Conclusions
exacerbated
specifically
This
adverse
effect
may
be
associated
mTOR.
study
implicates
should
avoided
AATD
patients.
Antioxidants,
Journal Year:
2023,
Volume and Issue:
13(1), P. 49 - 49
Published: Dec. 28, 2023
To
characterize
the
hits
from
a
phenotypic
neurotoxicity
screen,
we
obtained
transcriptomics
data
for
valinomycin,
diethylstilbestrol,
colchicine,
rotenone,
1-methyl-4-phenylpyridinium
(MPP),
carbaryl
and
berberine
(Ber).
For
all
compounds,
concentration
triggering
neurite
degeneration
correlated
with
onset
of
gene
expression
changes.
The
mechanistically
diverse
toxicants
caused
similar
patterns
regulation:
responses
were
dominated
by
cell
de-differentiation
canonical
stress
response
pathways
driven
ATF4
NRF2.
obtain
more
detailed
specific
information
on
modes-of-action,
effects
energy
metabolism
(respiration
glycolysis)
measured.
Ber,
rotenone
MPP
inhibited
mitochondrial
respiratory
chain
they
shared
complex
I
as
target.
This
group
was
further
evaluated
metabolomics
under
experimental
conditions
that
did
not
deplete
ATP.
Ber
(204
changed
metabolites)
showed
rotenone.
overall
metabolic
situation
characterized
oxidative
stress,
an
over-abundance
NADH
(>1000%
increase)
re-routing
in
order
to
dispose
nitrogen
resulting
increased
amino
acid
turnover.
unique
pattern
led
accumulation
metabolites
known
biomarkers
neurodegeneration
(saccharopine,
aminoadipate
branched-chain
ketoacids).
These
findings
suggest
inhibitors
may
result
ensemble
changes
rather
than
simple
ATP
depletion.
combi-omics
approach
used
here
provided
richer
MoA
common
analysis
alone.
As
human
drug
food
supplement,
mimicked
closely
mode-of-action
neurotoxicants,
its
potential
hazard
requires
investigation.
Cytoskeleton,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 11, 2024
Previous
reports
from
our
laboratory
describing
the
formation
of
myofibrils
in
cultured
embryonic
cardiac
and
skeletal
muscle
cells
have
proposed
that
myofibrillogenesis
occurs
three
steps
increasing
protein
organization:
beginning
with
premyofibrils,
followed
by
nascent
myofibrils,
ending
mature
myofibrils.
Inhibitors
ubiquitin
proteasome
system
(UPS)
prevented
progressing
directly
to
cells,
supporting
a
three-step
model
assembly
which
some
proteins
are
proteolyzed
allow
Application
UPS
inhibitors
on
suggests
possible
explanations
for
off-target
adverse
effects
drugs,
used
cancer
patients.
Berberine,
plant
derivative,
has
been
treat
various
cancers,
including
multiple
myelomas.
In
contrast
use
success
was
reported
Berberine
myeloma
patients
no
their
hearts.
We
exposed
ligase
inhibitor
UHRF1
(ubiquitin-like
PHD
RING
finger
domains).
inhibited
myofibril
at
stage
but
had
effect
heart
cells.
RT-PCR
experiments
demonstrated
inhibition
mRNA
myosin
II
heavy
chains
not
actin
is
also
being
as
popular
weight
losing
compound,
because
it
much
cheaper
available
without
prescription
than
semaglutide
containing
drugs
(Wegovy
Ozempic).
culture
assays
both
postulate
analyses
will
provide
preclinical
assay
testing
novel
improved
outcomes
patients,
an
important
goal
therapeutics.
Frontiers in Oncology,
Journal Year:
2024,
Volume and Issue:
14
Published: Dec. 2, 2024
Cancer
has
emerged
as
one
of
the
leading
causes
fatality
all
over
world.
Phytoconstituents
are
being
studied
for
their
synergistic
effects,
which
include
disease
prevention
by
altering
molecular
pathways
and
immunomodulation
without
side
effects.
The
present
experiment
aims
to
explore
cancer
preventive
activities
Nutrients,
Journal Year:
2024,
Volume and Issue:
16(24), P. 4415 - 4415
Published: Dec. 23, 2024
Background/Objectives:
Immune
checkpoints
are
essential
for
regulating
excessive
autoimmune
responses
and
maintaining
immune
homeostasis.
However,
in
the
tumor
microenvironment,
these
can
lead
to
cytotoxic
T
cell
exhaustion,
allowing
cancer
cells
evade
surveillance
promote
progression.
The
expression
of
programmed
death-ligand
1
(PD-L1)
is
associated
with
poor
prognoses,
reduced
survival
rates,
lower
therapies.
Consequently,
downregulating
PD-L1
has
become
a
key
strategy
developing
checkpoint
inhibitors
(ICIs).
Caryophylli
cortex
(CC),
derived
from
bark
clove
tree
Syzygium
aromaticum,
possesses
antioxidant
properties
against
cells,
yet
its
potential
as
an
ICI
remains
unclear.
Methods:
In
this
study,
we
aimed
investigate
whether
CC
extract
modulates
activates
immunity
through
co-culture
system
well
hPD-L1/MC-38
tumor-bearing
animal
models.
Results:
Our
findings
indicate
that
significantly
downregulated
both
constitutive
inducible
at
non-toxic
concentrations
while
simultaneously
enhancing
mortality
activity
system.
Furthermore,
administration
mice
resulted
greater
than
70%
reduction
growth
increased
infiltration
CD8+
within
microenvironment.
Principal
component
analysis
identified
bergenin,
chlorogenic
acid,
ellagic
acid
active
ICIs.
Conclusions:
These
suggest
exerts
potent
antitumor
effect
blocker
by
inhibiting
disrupting
PD-1/PD-L1
interaction.