bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2022,
Volume and Issue:
unknown
Published: Feb. 4, 2022
Abstract
The
ongoing
pandemic
of
coronavirus
disease
2019
(COVID-19)
has
made
a
serious
public
health
threat
globally.
To
discover
key
molecular
changes
in
COVID-19
and
its
secondary
complications,
we
analyzed
next-generation
sequencing
(NGS)
data
COVID-19.
NGS
(GSE163151)
was
screened
downloaded
from
the
Gene
Expression
Omnibus
database
(GEO).
Differentially
expressed
genes
(DEGs)
were
identified
present
study,
using
DESeq2
package
R
programming
software.
ontology
(GO)
pathway
enrichment
analysis
performed,
protein-protein
interaction
(PPI)
network,
module
analysis,
miRNA-hub
gene
regulatory
network
TF-hub
established.
Subsequently,
receiver
operating
characteristic
curve
(ROC)
used
to
validate
diagonostics
valuesof
hub
genes.
Firstly,
954
DEGs
(477
up
regulated
477
down
regulated)
four
dataset.
GO
revealed
related
immune
system
process
multicellular
organismal
process,
REACTOME
showed
formation
cornified
envelope.
Hub
PPI
network.
Furthermore,
ROC
indicate
that
complications
with
following
genes,
namely,
RPL10,
FYN,
FLNA,
EEF1A1,
UBA52,
BMI1,
ACTN2,
CRMP1,
TRIM42
PTCH1,
had
good
diagnostics
values.
This
study
several
associated
which
improves
our
knowledge
mechanism.
Chemical Research in Toxicology,
Journal Year:
2022,
Volume and Issue:
35(6), P. 1080 - 1094
Published: May 11, 2022
Insulin-secreting
β-cells
in
the
pancreatic
islets
are
exposed
to
various
endogenous
and
exogenous
stressing
conditions,
which
may
lead
β-cell
dysfunction
or
apoptosis
ultimately
diabetes
mellitus.
However,
detailed
molecular
mechanisms
underlying
β-cell's
inability
survive
under
severe
stresses
remain
be
explored.
This
study
used
two
common
chemical
stressors,
thapsigargin
rotenone,
induce
endoplasmic
reticulum
(ER)
mitochondria
stress
a
rat
insuloma
INS-1
832/13
line,
mimicking
conditions
experienced
by
dysfunctional
β-cells.
Proteomic
changes
of
cells
upon
treatment
with
stressors
at
IC50
were
profiled
TMT-based
quantitative
proteomics
further
verified
using
label-free
quantitive
proteomics.
The
differentially
expressed
proteins
selected
for
in-depth
bioinformatic
analysis.
Thapsigargin
specifically
perturbed
unfolded
protein
response
(UPR)
related
pathways;
addition,
58
not
previously
linked
UPR
pathways
identified
consistent
upregulation
induced
thapsigargin.
Conversely,
rotenone
resulted
significant
proteome
key
regulatory
such
as
fatty
acid
β-oxidation,
cellular
respiration,
citric
cycle,
respiratory
electron
transport.
Our
data
also
demonstrated
that
both
increased
reactive
oxygen
species
production
depleted
adenosine
triphosphate
synthesis,
resulting
dysregulation
oxidative
phosphorylation
signaling
pathways.
These
novel
dysregulated
suggest
an
alternative
mechanism
action
provide
potential
targets
probing
ER-
stress-induced
death.
BMC Medicine,
Journal Year:
2022,
Volume and Issue:
20(1)
Published: Sept. 23, 2022
Abstract
Background
Offspring
born
to
women
with
pregestational
type
1
diabetes
(T1DM)
are
exposed
an
intrauterine
hyperglycemic
milieu
and
has
increased
risk
of
metabolic
disease
later
in
life.
In
this
present
study,
we
hypothesize
that
utero
exposure
T1DM
alters
offspring
DNA
methylation
gene
expression,
thereby
altering
their
future
disease.
Methods
Follow-up
study
using
data
from
the
Epigenetic,
Genetic
Environmental
Effects
on
Growth,
Metabolism
Cognitive
Functions
Women
Type
Diabetes
(EPICOM)
collected
between
2012
2013.
Setting
Exploratory
sub-study
nationwide
EPICOM
study.
Participants
Adolescent
(
n
=20)
controls
matched
age,
sex,
postal
code.
Main
outcome
measures
This
investigates
450K-Illumina
Infinium
assay
RNA
expression
(RNA
sequencing)
leucocytes
peripheral
blood
samples.
Results
We
identified
9
hypomethylated
5
hypermethylated
positions
p
<
0.005,
|Δ
M
-value|
>
1)
38
up-
downregulated
genes
log2FC
≥
0.3)
adolescent
compared
controls.
None
these
findings
remained
significant
after
correction
for
multiple
testing.
However,
differences
co-expression
networks,
which
could
be
biological
significance,
weighted
correlation
network
analysis.
Interestingly,
one
modules
was
significantly
associated
T1DM.
Functional
enrichment
analysis,
changes
as
input,
revealed
ontologies
related
diabetes,
carbohydrate
glucose
metabolism,
pathways
including
MAPK1/MAPK3
MAPK
family
signaling,
T1DM,
obesity,
atherosclerosis,
vascular
pathologies.
Lastly,
by
integrating
data,
six
where
relevant
corresponded
CIITA
,
TPM1
PXN
ST8SIA1
LIPA
DAXX
).
Conclusions
These
suggest
possibility
maternal
impact
life
offspring,
a
profile
may
linked
Biomaterials Science,
Journal Year:
2022,
Volume and Issue:
11(4), P. 1470 - 1485
Published: Dec. 19, 2022
Pancreatic
islet
surface
engineering
has
been
proposed
as
an
"easy-to-adopt"
approach
to
enhance
post-transplantation
engraftment
for
treatment
against
diabetes.
Inulin
is
FDA-approved
dietary
prebiotic
with
reported
anti-diabetic,
anti-inflammatory,
anti-hypoxic
and
pro-angiogenic
properties.
We
therefore
assessed
whether
inulin
would
be
a
viable
option
engineering.
was
oxidized
generate
inulin-CHO,
which
bind
the
cell
membrane
via
covalent
bond
formation
between
-CHO
-NH2
across
membrane.
In
vitro
assessments
demonstrated
enhanced
viability
better
glucose-induced
insulin
secretion
from
inulin-coated
(5
mg
mL-1)
islets,
accompanied
by
revascularization,
shown
significantly
tube
branching
of
endothelial
MS1
cells
following
co-culture
islets.
Reduction
cytokine-induced
death
also
observed
islets
exposure
pro-inflammatory
cytokine
LPS.
LPS-induced
ROS
production
dampened
44%
in
when
compared
controls.
RNA-seq
analysis
control
identified
expression
alterations
genes
involved
function,
vascular
immune
regulation,
supporting
positive
impact
on
preservation.
vivo
examination
using
streptozotocin
(STZ)-induced
hyperglycemic
mice
further
showed
moderately
maintained
plasma
glucose
levels
received
transplantation
attributable
ameliorated
CD45+
infiltration
improved
graft
vascularization.
propose
safe
beneficial,
assessment
required
verify
its
applicability
clinical
transplantation.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: June 16, 2024
Abstract
The
pathogenesis
of
diabetes
involves
complex
changes
in
the
expression
profiles
mRNA
and
non-coding
RNAs
within
pancreatic
islet
cells.
Recent
progress
induced
pluripotent
stem
cell
(iPSC)
technology
have
allowed
modeling
diabetes-associated
genes.
Our
recent
study
using
FOXA2-deficient
human
iPSC
models
has
highlighted
an
essential
role
for
FOXA2
development
pancreas.
Here,
we
aimed
to
provide
further
insights
on
microRNAs
(miRNAs)
by
studying
miRNA-mRNA
regulatory
networks
iPSC-derived
islets
lacking
gene.
Consistent
with
our
previous
findings,
absence
significantly
downregulated
hormones,
INS,
GCG,
alongside
other
key
developmental
genes
islets.
Concordantly,
RNA-Seq
analysis
showed
significant
downregulation
related
upregulation
associated
nervous
system
lipid
metabolic
pathways.
Furthermore,
resulted
alterations
miRNA
expression,
61
miRNAs
upregulated
99
downregulated.
targeted
crucial
involved
development.
In
contrary,
a
network
targeting
metabolism.
These
findings
highlight
impact
suggesting
intricate
affecting
Stem Cell Reviews and Reports,
Journal Year:
2024,
Volume and Issue:
20(7), P. 1915 - 1931
Published: June 25, 2024
The
pathogenesis
of
diabetes
involves
complex
changes
in
the
expression
profiles
mRNA
and
non-coding
RNAs
within
pancreatic
islet
cells.
Recent
progress
induced
pluripotent
stem
cell
(iPSC)
technology
have
allowed
modeling
diabetes-associated
genes.
Our
recent
study
using
FOXA2-deficient
human
iPSC
models
has
highlighted
an
essential
role
for
FOXA2
development
pancreas.
Here,
we
aimed
to
provide
further
insights
on
microRNAs
(miRNAs)
by
studying
miRNA-mRNA
regulatory
networks
iPSC-derived
islets
lacking
gene.
Consistent
with
our
previous
findings,
absence
significantly
downregulated
hormones,
INS,
GCG,
alongside
other
key
developmental
genes
islets.
Concordantly,
RNA-Seq
analysis
showed
significant
downregulation
related
upregulation
associated
nervous
system
lipid
metabolic
pathways.
Furthermore,
resulted
alterations
miRNA
expression,
61
miRNAs
upregulated
99
downregulated.
targeted
crucial
involved
development.
In
contrary,
a
network
targeting
metabolism.
These
findings
highlight
impact
suggesting
intricate
affecting
Heliyon,
Journal Year:
2024,
Volume and Issue:
10(16), P. e36546 - e36546
Published: Aug. 1, 2024
Type
2
diabetes
(T2D)
and
hypertension
are
global
public
health
concerns
major
metabolic
disorders
in
humans.
Experimental
evidence
indicates
considerable
hereditary
influences
on
the
etiology
of
T2D
hypertension,
but
molecular
basis
these
diseases
is
still
limited.
Thus,
current
study
analyzed
185
(132
53
hypertension)
GWAS
catalog
datasets
identified
83
common
genes
linked
to
pathogenesis.
These
were
further
examined
using
various
bioinformatics
approaches
elucidate
their
mechanisms
underlying
pathophysiology
hypertension.
Gene
ontology
(GO)
analysis
revealed
biological,
cellular,
functions
genes,
which
also
different
pathways.
Specifically,
seven
found
be
crucial
for
T2D,
nine
directly
associated
with
Protein-protein
interaction
(PPI)
28
candidate
hub
through
11
topological
methods.
Among
231
miRNAs,
significant
interacting
transcription
factors
(TFs)
out
36
genes.
Additionally,
two
downregulated
by
43
FDA-approved
drugs.
findings
processes
suggesting
that
targeting
could
lead
future
drug
development
therapeutic
strategies
treat
Cureus,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 4, 2024
Background
Type
1
diabetes
(T1D)
is
an
autoimmune
disorder
that
results
in
the
destruction
of
pancreatic
beta
cells,
causing
a
shortage
insulin
secretion.
The
development
T1D
influenced
by
both
genetic
predisposition
and
environmental
factors,
such
as
vitamin
D.
This
known
for
its
ability
to
regulate
immune
system
has
been
associated
with
decreased
risk
T1D.
However,
specific
ways
which
D
affects
regulation
preservation
cells
are
not
yet
fully
understood.
Gaining
better
understanding
these
interactions
essential
identifying
potential
targets
preventing
treating
Methods
analysis
focused
on
two
Gene
Expression
Omnibus
(GEO)
datasets,
namely,
GSE55098
GSE50012,
detect
differentially
expressed
genes
(DEGs).
Enrichr
(Ma'ayan
Laboratory,
New
York,
NY)
was
used
perform
enrichment
Ontology
(GO)
biological
process
Kyoto
Encyclopedia
Genes
Genomes
(KEGG)
pathways.
Search
Tool
Retrieval
Interacting
12.0
(STRING)
database
generate
protein-protein
interaction
(PPI)
network.
Cytoscape
3.10.1
(Cytoscape
Team,
San
Diego,
CA)
analyze
PPI
network
discover
hub
genes.
Results
DEGs
datasets
were
identified
using
GEO2R
tool,
particular
focus
exhibiting
contrasting
regulations.
Enrichment
unveiled
participation
oppositely
regulated
processes
relevant
system.
revealed
five
genes,
MNDA,
LILRB2,
FPR2,
HCK,
FCGR2A,
suggesting
their
role
pathogenesis
response
Conclusion
study
elucidates
complex
between
metabolism
provide
important
knowledge
molecular
pathways
underlie
have
be
targeted
therapeutic
intervention.
research
underscores
importance
system's
modulation
impact
development.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2022,
Volume and Issue:
unknown
Published: Feb. 4, 2022
Abstract
The
ongoing
pandemic
of
coronavirus
disease
2019
(COVID-19)
has
made
a
serious
public
health
threat
globally.
To
discover
key
molecular
changes
in
COVID-19
and
its
secondary
complications,
we
analyzed
next-generation
sequencing
(NGS)
data
COVID-19.
NGS
(GSE163151)
was
screened
downloaded
from
the
Gene
Expression
Omnibus
database
(GEO).
Differentially
expressed
genes
(DEGs)
were
identified
present
study,
using
DESeq2
package
R
programming
software.
ontology
(GO)
pathway
enrichment
analysis
performed,
protein-protein
interaction
(PPI)
network,
module
analysis,
miRNA-hub
gene
regulatory
network
TF-hub
established.
Subsequently,
receiver
operating
characteristic
curve
(ROC)
used
to
validate
diagonostics
valuesof
hub
genes.
Firstly,
954
DEGs
(477
up
regulated
477
down
regulated)
four
dataset.
GO
revealed
related
immune
system
process
multicellular
organismal
process,
REACTOME
showed
formation
cornified
envelope.
Hub
PPI
network.
Furthermore,
ROC
indicate
that
complications
with
following
genes,
namely,
RPL10,
FYN,
FLNA,
EEF1A1,
UBA52,
BMI1,
ACTN2,
CRMP1,
TRIM42
PTCH1,
had
good
diagnostics
values.
This
study
several
associated
which
improves
our
knowledge
mechanism.
