Research Square (Research Square),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Sept. 19, 2023
Abstract
Background
-
Breast
cancer
(BC)
is
the
most
common
malignancy
with
very
high
incidence
and
relatively
mortality
in
women.
The
PIK3CA
gene
plays
a
pivotal
role
pathogenicity
of
breast
cancer.
Despite
these,
mutational
status
all
exons
except
9
20
still
remains
unknown.
Methods
This
study
uses
whole
exome
sequencing
(WES)
based
approach
to
identify
somatic
mutations
Indian
BC
cohorts.
resultant
hotspot
were
validated
by
droplet
digital
PCR
(ddPCR).
Further,
molecular
dynamics
(MD)
simulation
was
applied
elucidate
conformational
functional
effects
position
on
protein.
Results
In
our
cohort,
showed
44.4%
mutation
rate
among
top
mutated
genes.
confined
Exons
5,
9,
11,
18,
20,
whereas
maximum
number
lies
within
20.
A
total
variants
found
study,
which
2
novel
observed
(p.H554L)
11
(p.S629P).
However,
H1047R
at
exon
(20%).
tumor
tissues,
there
considerable
difference
between
copy
wild-type
mutant
detected
ddPCR.
Significant
structural
changes
during
MD
induced
due
point
H1047R/L
position.
Conclusions
current
provides
comprehensive
view
as
well
reported
single
nucleotide
(SNVs)
associated
cases.
could
serve
prognostic
value
terms
selecting
targeted
therapy
BC.
Biomolecules,
Journal Year:
2022,
Volume and Issue:
12(9), P. 1185 - 1185
Published: Aug. 26, 2022
There
have
been
magnificent
advancements
in
the
understanding
of
molecular
mechanisms
chronic
diseases
over
past
several
years,
but
these
continue
to
be
a
considerable
cause
death
worldwide.
Most
approved
medications
available
for
prevention
and
treatment
target
only
single
gene/protein/pathway
are
known
severe
side
effects
less
effective
than
they
anticipated.
Consequently,
development
finer
therapeutics
that
outshine
existing
ones
is
far-reaching.
Natural
compounds
enormous
applications
curbing
disastrous
fatal
diseases.
Oroxylin
A
(OA)
flavonoid
obtained
from
plants
Journal of Nanobiotechnology,
Journal Year:
2024,
Volume and Issue:
22(1)
Published: April 5, 2024
Abstract
Background
Osteoporosis
is
characterized
by
an
imbalance
in
bone
homeostasis,
resulting
the
excessive
dissolution
of
minerals
due
to
acidified
microenvironment
mediated
overactive
osteoclasts.
Oroxylin
A
(ORO),
a
natural
flavonoid,
has
shown
potential
reversing
osteoporosis
inhibiting
osteoclast-mediated
resorption.
The
limited
water
solubility
and
lack
targeting
specificity
hinder
effective
accumulation
within
pathological
environment
osteoporosis.
Results
Osteoclasts’
microenvironment-responsive
nanoparticles
are
prepared
incorporating
with
amorphous
calcium
carbonate
(ACC)
coated
glutamic
acid
hexapeptide-modified
phospholipids,
aiming
at
reinforcing
drug
delivery
efficiency
as
well
therapeutic
effect.
obtained
smart
nanoparticles,
coined
OAPLG,
could
instantly
neutralize
release
extracellular
combination
ACC
synergistically
inhibits
osteoclast
formation
activity,
leading
significant
reversal
systemic
loss
ovariectomized
mice
model.
Conclusion
work
highlights
intelligent
nanoplatform
based
on
for
spatiotemporally
controlled
lipophilic
drugs,
illustrates
prominent
promise
against
Frontiers in Pharmacology,
Journal Year:
2023,
Volume and Issue:
14
Published: Sept. 12, 2023
Oxidative
stress
(OS)
is
a
pathological
status
that
occurs
when
the
body’s
balance
between
oxidants
and
antioxidant
defense
systems
broken,
which
can
promote
development
of
many
diseases.
Nrf2,
redox-sensitive
transcription
encoded
by
NFE2L2,
master
regulator
phase
II
enzymes
cytoprotective
genes.
In
this
context,
Nrf2/ARE
signaling
be
compelling
target
against
OS-induced
Recently,
natural
regulators
like
dietary
flavones
have
shown
therapeutic
potential
in
various
acute
chronic
diseases
such
as
diabetes,
neurodegenerative
diseases,
ischemia-reperfusion
injury,
cancer.
review,
we
aim
to
summarize
nrf2-mediated
protective
effects
different
conditions.
Firstly,
retrospected
mechanisms
how
regulate
pathway
introduced
mediator
role
Nrf2
plays
inflammation
apoptosis.
Then
review
evidence
modulated
prevent
experimental
models.
Based
on
these
literature,
found
could
expression
below:
1)
dissociating
binding
Keap1
via
PKC-mediated
phosphorylation
P62-mediated
autophagic
degradation;
2)
regulating
nuclear
translocation
kinases
AMPK,
MAPKs,
Fyn;
3)
decreasing
ubiquitination
degradation
activating
sirt1
PI3K/AKT-mediated
GSK3
inhibition;
4)
epigenetic
alternation
demethylation
at
promoter
region
histone
acetylation.
conclusion,
targeting
promising
agents
for
OS-related
disorders.
However,
there
lack
investigations
human
subjects,
new
drug
delivery
improve
flavones’
treatment
efficiency
still
need
developed.
Pharmacological Research,
Journal Year:
2024,
Volume and Issue:
203, P. 107167 - 107167
Published: April 9, 2024
Cancer
has
become
a
burgeoning
global
healthcare
concern
marked
by
its
exponential
growth
and
significant
economic
ramifications.
Though
advancements
in
the
treatment
modalities
have
increased
overall
survival
quality
of
life,
there
are
no
definite
treatments
for
advanced
stages
this
malady.
Hence,
understanding
diseases
etiologies
underlying
molecular
complexities,
will
usher
development
innovative
therapeutics.
Recently,
YAP/TAZ
transcriptional
regulation
been
immense
interest
due
to
their
role
development,
tissue
homeostasis
oncogenic
transformations.
axis
functions
as
coactivators
within
Hippo
signaling
cascade,
exerting
pivotal
influence
on
processes
such
proliferation,
regeneration,
renewal.
In
cancer,
YAP
is
overexpressed
multiple
tumor
types
associated
with
cancer
stem
cell
attributes,
chemoresistance,
metastasis.
Activation
mirrors
cellular
"social"
behavior,
encompassing
factors
adhesion
mechanical
signals
transmitted
from
structure
surrounding
extracellular
matrix.
Therefore,
it
presents
vulnerability
clogs
tumors
that
could
provide
wide
window
therapeutic
effectiveness.
Natural
compounds
utilized
extensively
successful
interventions
management
diverse
chronic
illnesses,
including
cancer.
Owing
capacity
genes
pathways,
natural
exhibit
potential
either
adjuvant
therapy
or
combination
conventional
options.
review,
we
delineate
nexus
axis,
present
an
alternate
strategy
target
Frontiers in Pharmacology,
Journal Year:
2023,
Volume and Issue:
14
Published: June 1, 2023
Ulcerative
colitis
(UC)
is
a
chronic
aspecific
gut
inflammatory
disorder
that
primarily
involves
the
recta
and
colons.
It
mostly
presents
as
long
course
of
repeated
attacks.
This
disease,
characterized
by
intermittent
diarrhoea,
fecal
blood,
stomachache,
tenesmus,
severely
decreases
living
quality
sick
persons.
UC
difficult
to
heal,
has
high
recurrence
rate,
tightly
related
incidence
colon
cancer.
Although
there
are
number
drugs
available
for
suppression
colitis,
conventional
therapy
possesses
certain
limitations
severe
adverse
reactions.
Thus,
it
extremely
required
safe
effective
medicines
naturally
derived
flavones
exhibited
huge
prospects.
study
focused
on
advancement
from
edible
pharmaceutical
plants
treating
colitis.
The
underlying
mechanisms
natural-derived
in
were
closely
linked
regulation
enteric
barrier
function,
immune-inflammatory
responses,
oxidative
stress,
microflora,
SCFAs
production.
prominent
effects
safety
make
them
promising
candidate
treatment.
Cellular and Molecular Life Sciences,
Journal Year:
2024,
Volume and Issue:
81(1)
Published: Feb. 9, 2024
Abstract
Hematological
malignancies
(HM)
represent
a
subset
of
neoplasms
affecting
the
blood,
bone
marrow,
and
lymphatic
systems,
categorized
primarily
into
leukemia,
lymphoma,
multiple
myeloma.
Their
prognosis
varies
considerably,
with
frequent
risk
relapse
despite
ongoing
treatments.
While
contemporary
therapeutic
strategies
have
extended
overall
patient
survival,
they
do
not
offer
cures
for
advanced
stages
often
lead
to
challenges
such
as
acquisition
drug
resistance,
recurrence,
severe
side
effects.
The
need
innovative
targets
is
vital
elevate
both
survival
rates
patients'
quality
life.
Recent
research
has
pivoted
towards
nuclear
receptors
(NRs)
due
their
role
in
modulating
tumor
cell
characteristics
including
uncontrolled
proliferation,
differentiation,
apoptosis
evasion,
invasion
migration.
Existing
evidence
emphasizes
NRs'
critical
HM.
regulation
NR
expression
through
agonists,
antagonists,
or
selective
modulators,
contingent
upon
levels,
offers
promising
clinical
implications
HM
management.
Moreover,
several
anticancer
agents
targeting
NRs
been
approved
by
Food
Drug
Administration
(FDA).
This
review
highlights
integral
function
HM's
pathophysiology
potential
benefits
therapeutically
these
receptors,
suggesting
prospective
avenue
more
efficient
interventions
against
Graphical
abstract
Discover Oncology,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Feb. 19, 2024
Abstract
Colorectal
cancer
(CRC)
stands
as
one
of
the
most
prevalent
form
globally,
causing
a
significant
number
deaths,
surpassing
0.9
million
in
year
2020.
According
to
GLOBOCAN
2020,
CRC
ranks
third
incidence
and
second
mortality
both
males
females.
Despite
extensive
studies
over
years,
there
is
still
need
establish
novel
therapeutic
targets
enhance
patients’
survival
rate
CRC.
Nuclear
receptors
(NRs)
are
ligand-activated
transcription
factors
(TFs)
that
regulate
numerous
essential
biological
processes
such
differentiation,
development,
physiology,
reproduction,
cellular
metabolism.
Dysregulation
anomalous
expression
different
NRs
has
led
multiple
alterations,
impaired
signaling
cascades,
mutations,
epigenetic
changes,
leading
various
diseases,
including
cancer.
It
been
observed
differential
might
lead
initiation
progression
CRC,
correlated
with
poor
outcomes
patients.
on
mechanism
role
this
cancer,
it
remains
scientific
interest
primarily
due
diverse
functions
exhibit
regulating
key
hallmarks
Thus,
modulating
their
agonists
antagonists,
based
levels,
holds
an
immense
prospect
diagnosis,
prognosis,
therapeutical
modalities
In
review,
we
focus
pathogenesis
emphasized
significance
targeting
these
using
variety
agents,
which
may
represent
effective
strategy
for
prevention
treatment
Graphical
