TY  - JOUR
A1  - Alnusaire, Taghreed S.
A1  - Sayed, Ahmed M.
A1  - Elmaidomy, Abeer H.
A1  - Al-Sanea, Mohammad M.
A1  - Albogami, Sarah
A1  - Albqmi, Mha
A1  - Alowaiesh, Bassam F.
A1  - Mostafa, Ehab M.
A1  - Musa, Arafa
A1  - Youssif, Khayrya A.
A1  - Refaat, Hesham
A1  - Othman, Eman M.
A1  - Dandekar, Thomas
A1  - Alaaeldin, Eman
A1  - Ghoneim, Mohammed M.
A1  - Abdelmohsen, Usama Ramadan
T1  - An in vitro and in silico study of the enhanced antiproliferative and pro-oxidant potential of Olea europaea L. cv. Arbosana leaf extract via elastic nanovesicles (spanlastics)
JF  - Antioxidants
N2  - The olive tree is a venerable Mediterranean plant and often used in traditional medicine. The main aim of the present study was to evaluate the effect of Olea europaea L. cv. Arbosana leaf extract (OLE) and its encapsulation within a spanlastic dosage form on the improvement of its pro-oxidant and antiproliferative activity against HepG-2, MCF-7, and Caco-2 human cancer cell lines. The LC-HRESIMS-assisted metabolomic profile of OLE putatively annotated 20 major metabolites and showed considerable in vitro antiproliferative activity against HepG-2, MCF-7, and Caco-2 cell lines with IC\(_{50}\) values of 9.2 ± 0.8, 7.1 ± 0.9, and 6.5 ± 0.7 µg/mL, respectively. The encapsulation of OLE within a (spanlastic) nanocarrier system, using a spraying method and Span 40 and Tween 80 (4:1 molar ratio), was successfully carried out (size 41 ± 2.4 nm, zeta potential 13.6 ± 2.5, and EE 61.43 ± 2.03%). OLE showed enhanced thermal stability, and an improved in vitro antiproliferative effect against HepG-2, MCF-7, and Caco-2 (IC\(_{50}\) 3.6 ± 0.2, 2.3 ± 0.1, and 1.8 ± 0.1 µg/mL, respectively) in comparison to the unprocessed extract. Both preparations were found to exhibit pro-oxidant potential inside the cancer cells, through the potential inhibitory activity of OLE against glutathione reductase and superoxide dismutase (IC\(_{50}\) 1.18 ± 0.12 and 2.33 ± 0.19 µg/mL, respectively). These inhibitory activities were proposed via a comprehensive in silico study to be linked to the presence of certain compounds in OLE. Consequently, we assume that formulating such a herbal extract within a suitable nanocarrier would be a promising improvement of its therapeutic potential.
KW  - olive
KW  - metabolomic profiling
KW  - antiproliferative
KW  - pro-oxidant
KW  - encapsulation
KW  - spanlastic
KW  - nanocarrier
KW  - docking
KW  - molecular dynamics simulation
KW  - Olea
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250064
SN  - 2076-3921
VL  - 10
IS  - 12
ER  - 
TY  - JOUR
A1  - Breitenbach, Tim
A1  - Helfrich-Förster, Charlotte
A1  - Dandekar, Thomas
T1  - An effective model of endogenous clocks and external stimuli determining circadian rhythms
JF  - Scientific Reports
N2  - Circadian endogenous clocks of eukaryotic organisms are an established and rapidly developing research field. To investigate and simulate in an effective model the effect of external stimuli on such clocks and their components we developed a software framework for download and simulation. The application is useful to understand the different involved effects in a mathematical simple and effective model. This concerns the effects of Zeitgebers, feedback loops and further modifying components. We start from a known mathematical oscillator model, which is based on experimental molecular findings. This is extended with an effective framework that includes the impact of external stimuli on the circadian oscillations including high dose pharmacological treatment. In particular, the external stimuli framework defines a systematic procedure by input-output-interfaces to couple different oscillators. The framework is validated by providing phase response curves and ranges of entrainment. Furthermore, Aschoffs rule is computationally investigated. It is shown how the external stimuli framework can be used to study biological effects like points of singularity or oscillators integrating different signals at once. The mathematical framework and formalism is generic and allows to study in general the effect of external stimuli on oscillators and other biological processes. For an easy replication of each numerical experiment presented in this work and an easy implementation of the framework the corresponding Mathematica files are fully made available. They can be downloaded at the following link: https://www.biozentrum.uni-wuerzburg.de/bioinfo/computing/circadian/.
KW  - computational biology and bioinformatics
KW  - systems biology
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261655
VL  - 11
IS  - 1
ER  - 
TY  - JOUR
A1  - Dandekar, Thomas
A1  - Argos, Patrick
T1  - Amiloride-sensitive epithelial Na\(^+\) channel is made of three homologous subunits
N2  - No abstract available
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-29734
ER  - 
TY  - JOUR
A1  - Gupta, Shishir K.
A1  - Srivastava, Mugdha
A1  - Minocha, Rashmi
A1  - Akash, Aman
A1  - Dangwal, Seema
A1  - Dandekar, Thomas
T1  - Alveolar regeneration in COVID-19 patients: a network perspective
JF  - International Journal of Molecular Sciences
N2  - A viral infection involves entry and replication of viral nucleic acid in a host organism, subsequently leading to biochemical and structural alterations in the host cell. In the case of SARS-CoV-2 viral infection, over-activation of the host immune system may lead to lung damage. Albeit the regeneration and fibrotic repair processes being the two protective host responses, prolonged injury may lead to excessive fibrosis, a pathological state that can result in lung collapse. In this review, we discuss regeneration and fibrosis processes in response to SARS-CoV-2 and provide our viewpoint on the triggering of alveolar regeneration in coronavirus disease 2019 (COVID-19) patients.
KW  - COVID-19
KW  - SARS-CoV-2
KW  - alveolar regeneration
KW  - alveolar fibrosis
KW  - signaling pathway
KW  - network biology
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284307
SN  - 1422-0067
VL  - 22
IS  - 20
ER  - 
TY  - JOUR
A1  - Dandekar, Thomas
A1  - Gramsch, Christian
A1  - Houghton, Richard A.
A1  - Schultz, Rüdiger
T1  - Affinity purification of \(\beta\)-endorphin-like material from NG108CC15 cells by means of the monoclonal \(\beta\)-endorphin antibody 3-E7
N2  - No abstract available
Y1  - 1985
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-29896
ER  - 
TY  - JOUR
A1  - Rackevei, Antonia S.
A1  - Borges, Alyssa
A1  - Engstler, Markus
A1  - Dandekar, Thomas
A1  - Wolf, Matthias
T1  - About the analysis of 18S rDNA sequence data from trypanosomes in barcoding and phylogenetics: tracing a continuation error occurring in the literature
JF  - Biology
N2  - The variable regions (V1–V9) of the 18S rDNA are routinely used in barcoding and phylogenetics. In handling these data for trypanosomes, we have noticed a misunderstanding that has apparently taken a life of its own in the literature over the years. In particular, in recent years, when studying the phylogenetic relationship of trypanosomes, the use of V7/V8 was systematically established. However, considering the current numbering system for all other organisms (including other Euglenozoa), V7/V8 was never used. In Maia da Silva et al. [Parasitology 2004, 129, 549–561], V7/V8 was promoted for the first time for trypanosome phylogenetics, and since then, more than 70 publications have replicated this nomenclature and even discussed the benefits of the use of this region in comparison to V4. However, the primers used to amplify the variable region of trypanosomes have actually amplified V4 (concerning the current 18S rDNA numbering system).
KW  - RNA secondary structure
KW  - variable regions
KW  - V1–V9
KW  - V4
KW  - V7/V8
KW  - Trypanosoma
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297562
SN  - 2079-7737
VL  - 11
IS  - 11
ER  - 
TY  - JOUR
A1  - Göttlich, Claudia
A1  - Kunz, Meik
A1  - Zapp, Cornelia
A1  - Nietzer, Sarah L.
A1  - Walles, Heike
A1  - Dandekar, Thomas
A1  - Dandekar, Gudrun
T1  - A combined tissue-engineered/in silico signature tool patient stratification in lung cancer
JF  - Molecular Oncology
N2  - Patient-tailored therapy based on tumor drivers is promising for lung cancer treatment. For this, we combined in vitro tissue models with in silico analyses. Using individual cell lines with specific mutations, we demonstrate a generic and rapid stratification pipeline for targeted tumor therapy. We improve in vitro models of tissue conditions by a biological matrix-based three-dimensional (3D) tissue culture that allows in vitro drug testing: It correctly shows a strong drug response upon gefitinib (Gef) treatment in a cell line harboring an EGFR-activating mutation (HCC827), but no clear drug response upon treatment with the HSP90 inhibitor 17AAG in two cell lines with KRAS mutations (H441, A549). In contrast, 2D testing implies wrongly KRAS as a biomarker for HSP90 inhibitor treatment, although this fails in clinical studies. Signaling analysis by phospho-arrays showed similar effects of EGFR inhibition by Gef in HCC827 cells, under both 2D and 3D conditions. Western blot analysis confirmed that for 3D conditions, HSP90 inhibitor treatment implies different p53 regulation and decreased MET inhibition in HCC827 and H441 cells. Using in vitro data (western, phospho-kinase array, proliferation, and apoptosis), we generated cell line-specific in silico topologies and condition-specific (2D, 3D) simulations of signaling correctly mirroring in vitro treatment responses. Networks predict drug targets considering key interactions and individual cell line mutations using the Human Protein Reference Database and the COSMIC database. A signature of potential biomarkers and matching drugs improve stratification and treatment in KRAS-mutated tumors. In silico screening and dynamic simulation of drug actions resulted in individual therapeutic suggestions, that is, targeting HIF1A in H441 and LKB1 in A549 cells. In conclusion, our in vitro tumor tissue model combined with an in silico tool improves drug effect prediction and patient stratification. Our tool is used in our comprehensive cancer center and is made now publicly available for targeted therapy decisions.
KW  - 3D lung tumor model
KW  - Boolean signaling network
KW  - chemoresistance
KW  - HSP90 inhibitor
KW  - insilico drug screening too
KW  - KRAS mutation signature
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233137
VL  - 12
ER  -