Drug Metabolism and Disposition,
Год журнала:
2020,
Номер
48(5), С. 395 - 406
Опубликована: Фев. 29, 2020
Dependence
of
drug
metabolism
on
dosing
time
has
long
been
recognized.
However,
only
recently
are
the
underlying
mechanisms
for
circadian
being
clarified.
Diurnal
rhythmicity
in
expression
drug-metabolizing
enzymes
is
believed
to
be
a
key
factor
determining
metabolism.
Supporting
notion
that
biological
rhythms
generated
and
maintained
by
clock,
number
diurnal
under
control
clock.
In
general,
clock
genes
generate
regulate
via
transcriptional
actions
one
or
two
three
cis-elements
(i.e.,
E-box,
D-box,
Rev-erb
response
element
RAR-related
orphan
receptor
element).
Additionally,
cycling
clock-controlled
nuclear
receptors
such
as
hepatocyte
4α
peroxisome
proliferator–activated
γ
contributors
enzyme
expression.
These
newly
discovered
each
rhythmic
reviewed
this
article.
We
also
discuss
how
translated
pharmacokinetics
chronotoxicity,
which
direct
implications
chronotherapeutics.
Our
discussion
extended
transporters
(P-glycoprotein
multidrug
resistance-associated
protein
2)
have
an
important
role
absorption.
Although
experimental
evidence
lacking
metabolism-based
chronoefficacy,
(e.g.,
Rev-erbα)
targets
shown
account
variability
efficacy.
SIGNIFICANCE
STATEMENT
Significant
progress
made
understanding
molecular
generation
enzymes.
article,
we
review
Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Апрель 13, 2021
Abstract
The
integration
of
single
cell
transcriptome
and
chromatin
accessibility
datasets
enables
a
deeper
understanding
heterogeneity.
We
performed
nucleus
ATAC
(snATAC-seq)
RNA
(snRNA-seq)
sequencing
to
generate
paired,
cell-type-specific
transcriptional
profiles
the
adult
human
kidney.
demonstrate
that
snATAC-seq
is
comparable
snRNA-seq
in
assignment
identity
can
further
refine
our
functional
heterogeneity
nephron.
majority
differentially
accessible
regions
are
localized
promoters
significant
proportion
closely
associated
with
expressed
genes.
Cell-type-specific
enrichment
transcription
factor
binding
motifs
implicates
activation
NF-κB
promotes
VCAM1
expression
drives
transition
between
subpopulation
proximal
tubule
epithelial
cells.
Our
multi-omics
approach
improves
ability
detect
unique
states
within
kidney
redefines
cellular
thick
ascending
limb.
Plant Biotechnology Journal,
Год журнала:
2022,
Номер
20(11), С. 2135 - 2148
Опубликована: Июль 23, 2022
Improving
biological
nitrogen
fixation
(BNF)
in
cereal
crops
is
a
long-sought
objective;
however,
no
successful
modification
of
showing
increased
BNF
has
been
reported.
Here,
we
described
novel
approach
which
rice
plants
were
modified
to
increase
the
production
compounds
that
stimulated
biofilm
formation
soil
diazotrophic
bacteria,
promoted
bacterial
colonization
plant
tissues
and
improved
with
grain
yield
at
limiting
contents.
We
first
used
chemical
screening
identify
plant-produced
induced
nitrogen-fixing
bacteria
demonstrated
apigenin
other
flavones
BNF.
then
CRISPR-based
gene
editing
targeting
breakdown
rice,
increasing
contents
root
exudation.
When
grown
conditions,
displayed
yield.
Biofilm
also
microbiome
structure,
favouring
enrichment
recruitment.
Our
results
support
manipulation
flavone
biosynthetic
pathway
as
feasible
strategy
for
induction
cereals
reduction
use
inorganic
fertilizers.
Disorder
in
bile
acid
(BA)
metabolism
is
known
to
be
an
important
factor
contributing
diarrhea.
However,
the
pathogenesis
of
BA
disorder-induced
diarrhea
remains
unclear.
The
colonic
pool
and
microbiota
between
health
piglets
diarrheal
were
compared.
Fecal
transplantation
various
cell
experiments
further
indicated
that
chenodeoxycholic
(CDCA)
metabolic
disorder
produced
CDCA-3β-glucuronide,
which
main
cause
Non-targeted
metabolomics
uncovered
inhibition
glucuronidation
by
Lactobacillus
reuteri
(L.
reuteri)
through
deriving
indole-3-carbinol
(I3C).
In
vitro,
gene
involved
reduction
induced-diarrhea
screened
RNA
transcriptomics
sequencing,
activation
pathway
FXR-SIRT1-LKB1
alleviate
P53-mediated
apoptosis
proposed
vitro
multifarious
siRNA
interference,
CO-IP,
immunofluorescence,
so
on,
mechanism
was
also
verified
a
variety
mouse
models.
Here,
we
reveal
for
first
time
core
derived
I3C
represses
gut
epithelium
glucuronidation,
particularly
3β-glucuronic
CDCA
production,
reaction
mediated
host
UDP
glucuronosyltransferase
family
1
member
A4
(UGT1A4)
necessary
induced
Mechanistically,
L.
activates
aryl
hydrocarbon
receptor
decrease
UGT1A4
transcription
CDCA-3β-glucuronide
content,
thereby
upregulating
signal.
LKB1
binds
with
P53
based
on
protein
interaction,
ultimately
resists
Moreover,
assists
attain
ameliorative
effects
FXR
diarrhea,
reversion
abnormal
pathway,
improving
outcomes
supplement.
These
findings
uncover
crucial
interplay
epithelial
cells
microbes,
highlighting
UGT1A4-mediated
conversion
as
key
target
ameliorating
British Journal of Cancer,
Год журнала:
2020,
Номер
122(9), С. 1277 - 1287
Опубликована: Фев. 12, 2020
Abstract
The
best-known
role
of
UDP-glucuronosyltransferase
enzymes
(UGTs)
in
cancer
is
the
metabolic
inactivation
drug
therapies.
By
conjugating
glucuronic
acid
to
lipophilic
drugs,
UGTs
impair
biological
activity
and
enhance
water
solubility
these
agents,
driving
their
elimination.
Multiple
clinical
observations
support
an
expanding
for
as
modulators
response
mediating
resistance
numerous
types.
However,
accumulating
evidence
also
suggests
influence
UGT
pathway
on
progression.
Dysregulation
expression
has
been
associated
with
progression
several
cancers,
arguing
possible
mediators
oncogenic
pathways
and/or
disease
accelerators
a
drug-naive
context.
consequences
altered
tumour
biology
are
incompletely
understood.
They
might
be
perturbed
levels
bioactive
endogenous
metabolites
such
steroids
lipids
that
inactivated
by
or
through
non-enzymatic
mechanisms,
thereby
eliciting
signalling
cascades.
This
review
highlights
supporting
dual
roles
pathway,
affecting
resistance.
Pharmacogenomic
testing
profiles
patients
development
therapeutic
options
actions
could
provide
useful
prognostic
predictive
biomarkers
efficacy
anti-cancer
drugs.
Natural Product Reports,
Год журнала:
2021,
Номер
39(3), С. 474 - 511
Опубликована: Сен. 28, 2021
Covering:
1928-2021Ginkgo
biloba
L.
is
one
of
the
most
distinctive
plants
to
have
emerged
on
earth
and
has
no
close
living
relatives.
Owing
its
phylogenetic
divergence
from
other
plants,
G.
contains
many
compounds
with
unique
structures
that
served
broaden
chemical
diversity
herbal
medicine.
Examples
such
include
terpene
trilactones
(ginkgolides),
acylated
flavonol
glycosides
(ginkgoghrelins),
biflavones
(ginkgetin),
ginkgotides
ginkgolic
acids.
The
extract
leaf
used
prevent
and/or
treat
cardiovascular
diseases,
while
ginkgo-derived
are
currently
at
various
stages
preclinical
clinical
trials
worldwide.
global
annual
sales
products
estimated
total
US$10
billion.
However,
content
purity
active
isolated
by
traditional
methods
usually
low
subject
varying
environmental
factors,
making
it
difficult
meet
huge
demand
international
market.
This
highlights
need
develop
new
strategies
for
preparation
these
characteristic
biloba.
In
this
review,
we
provide
a
detailed
description
bioactivities
summarize
recent
research
development
synthesis,
biosynthesis,
biotechnological
production
terpenoids,
flavonoids,
alkylphenols/alkylphenolic
acids
Our
aim
an
important
point
reference
all
scientists
who
ginkgo-related
medicinal
or
purposes.
Journal of Toxicology and Environmental Health Part B,
Год журнала:
2021,
Номер
24(2), С. 51 - 94
Опубликована: Фев. 17, 2021
Caenorhabditis
elegans
has
emerged
as
a
major
model
in
biomedical
and
environmental
toxicology.
Numerous
papers
on
toxicology
pharmacology
C.
have
been
published,
this
species
now
adopted
by
investigators
academic
toxicology,
pharmacology,
drug
discovery
labs.
also
attracted
the
interest
of
governmental
regulatory
agencies
charged
with
evaluating
safety
chemicals.
However,
major,
fundamental
aspect
toxicological
science
remains
underdeveloped
elegans:
xenobiotic
metabolism
transport
processes
that
are
critical
to
understanding
toxicokinetics
toxicodynamics,
extrapolation
other
species.
The
aim
review
was
initially
briefly
describe
history
trajectory
use
pharmacological
studies.
Subsequently,
physical
barriers
chemical
uptake
role
worm
microbiome
transformation
were
described.
Then
what
is
not
known
regarding
classic
Phase
I,
II,
III
performed.
In
addition,
following
discussed
(1)
regulation
metabolism;
(2)
published
for
specific
chemicals;
(3)
genetic
diversity
these
elegans.
Finally,
placed
an
evolutionary
context;
key
areas
future
research
highlighted;
implications
extrapolating
toxicity
results
discussed.
Computational and Structural Biotechnology Journal,
Год журнала:
2020,
Номер
18, С. 1383 - 1390
Опубликована: Янв. 1, 2020
Highlights•The
phylogenetic
distribution
of
GT1
family
enzymes
showed
domain-dependent
pattern.•The
characterized
GTs
distinct
substrates
spectrum.•Two
regions
that
discriminate
the
from
different
domains
were
identified.Graphical
abstractAbstractGlycosyltransferases
(GTs)
are
responsible
for
transferring
glycosyl
moieties
activated
sugar
donors
to
certain
acceptors,
among
which
have
been
known
their
outstanding
glycosylation
capacities
toward
diverse
natural
products,
such
as
glycolipids,
flavonoids
and
macrolides
etc.
However,
there
still
lacks
a
systematic
collation
this
important
members.
In
minireview,
all
sequences
phylogenetically
analyzed,
grouping
proteins
exhibited
taxonomic
life
pattern,
revealing
many
untapped
clades
GTs.
The
further
analysis
facilitated
classification
coverage
domains,
whereby
bacteria
can
tolerate
wider
spectrum
chemical
skeletons
substrates,
showing
higher
promiscuity
than
those
other
domains.
Furthermore,
sequence
sizes
compared
understand
selectivity.
Based
on
multiple
alignments
28
representative
with
crystal
structures,
two
critical
located
in
N-terminal
identified,
most
variable
essential
binding
and/or
catalysis.
key
roles
these
validated
by
enumerating
influential
residues
interacted
structures
plants.
atlas
terms
phylogeny,
selectivity,
length,
motifs
provides
clues
exploration
unknown
GT1s
rational
engineering
enzymes,
synthesizing
novel
promising
glycoconjugates
pharmaceutical
application.
Basic & Clinical Pharmacology & Toxicology,
Год журнала:
2022,
Номер
131(5), С. 311 - 324
Опубликована: Авг. 16, 2022
Safe
and
effective
use
of
drugs
requires
an
understanding
metabolism
transport.
We
identified
the
100
most
prescribed
in
six
countries
conducted
a
literature
search
on
vitro
data
to
assess
contribution
Phase
I
II
enzymes
drug
transporters
Eighty-nine
undergo
or
are
known
substrates
for
transporters.
involved
67
drugs,
while
mediate
18
drugs.
CYP3A4/5
is
important
enzyme
43
followed
by
CYP2D6
(23
drugs),
CYP2C9
CYP2C19
(22
CYP1A2
(14
drugs)
CYP2C8
(11
drugs).
More
than
half
(54
P-glycoprotein
(P-gp)
be
transport
30
breast
cancer
resistance
protein
(BCRP)
facilitates
11
A
considerable
proportion
subject
combination
metabolism,
and/or
conclude
that
majority
frequently
depend
Thus,
variability
remains
priority.