TY - JOUR A1 - Grebinyk, Anna A1 - Yashchuk, Valeriy A1 - Bashmakova, Nataliya A1 - Gryn, Dmytro A1 - Hagemann, Tobias A1 - Naumenko, Antonina A1 - Kutsevol, Nataliya A1 - Dandekar, Thomas A1 - Frohme, Marcus T1 - A new triple system DNA-Nanosilver-Berberine for cancer therapy JF - Applied Nanoscience N2 - The isoquinoline quaternary alkaloid Berberine possesses a variety of pharmacological properties that suggests its promising application for an anticancer delivery system design utilizing its ability to intercalate DNA. In the current work, we have investigated the effects of Berberine on the human T cell leukemia cell line in vitro. Fluorescent microscopy of leukemic cells revealed Berberine nuclear localization. The results showed that Berberine inhibited leukemic cell growth in a time- and dose-dependent manner, that was associated with reactive oxygen species production intensification and caspase 3/7 activity increase with followed apoptosis induction. Berberine was used as a toxic and phototoxic agent for triple system synthesis along with DNA as a carrier and nanosilver as a plasmonic accelerator of Berberine electronic transitions and high energy emission absorbent centers. The proposed method allows to obtain the complex of DNA with Berberine molecules and silver nanoparticles. The optical properties of free components as well as their various combinations, including the final triple system DNA-Nanosilver-Berberine, were investigated. Obtained results support the possibility to use the triple system DNA-Nanosilver-Berberine as an alternative therapeutic agent for cancer treatment. Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-16105 SN - 2190-5517 VL - 9 SP - 945 EP - 956 PB - Springer ER - TY - JOUR A1 - Grebinyk, Anna A1 - Yashchuk, Valeriy A1 - Bashmakova, Nataliya A1 - Gryn, Dmytro A1 - Hagemann, Tobias A1 - Naumenko, Antonina A1 - Kutsevol, Nataliya A1 - Dandekar, Thomas A1 - Frohme, Marcus T1 - A New Triple System DNA-Nanosilver-Berberine for Cancer Therapy JF - Applied Nanoscience N2 - The isoquinoline quaternary alkaloid Berberine possesses a variety of pharmacological properties that suggests its promising application for an anticancer delivery system design utilizing its ability to intercalate DNA.In the current work we have investigated the effects of Berberine on the human T-cell leukemia cell line in vitro.Fluorescent microscopy of leukemic cells revealed Berberine nuclear localization. The results showed that Berberine inhibited leukemic cell growth in a time-and dose-dependent manner, that was associated with reactive oxygen species production intensification and caspase 3/7 activity increase with followed apoptosis induction.Berberine was used as a toxic and phototoxic agent for triple system synthesis along with DNA as a carrier and nanosilver as a plasmonic accelerator of Berberine electronic transitions and high energy emission absorbent centers.The proposed method allows to obtain the complex of DNA with Berberine molecules and silver nanopoarticles. The optical properties of free components as well as their various combinations, including the final triple system DNA-Nanosilver-Berberine, were investigated. Obtained results support the possibility to use the triple system DNA-Nanosilver-Berberine as an alternative therapeutic agent for cancer treatment. KW - berberine KW - apoptosis KW - nanosilver KW - DNA delivery system Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-10628 SN - 2190-5517 ER - TY - JOUR A1 - Kagel, Heike A1 - Bier, Frank Fabian A1 - Frohme, Marcus A1 - Glökler, Jörn T1 - A Novel Optical Method To Reversibly Control Enzymatic Activity Based On Photoacids JF - Scientific Reports N2 - Most biochemical reactions depend on the pH value of the aqueous environment and some are strongly favoured to occur in an acidic environment. A non-invasive control of pH to tightly regulate such reactions with defined start and end points is a highly desirable feature in certain applications, but has proven difficult to achieve so far. We report a novel optical approach to reversibly control a typical biochemical reaction by changing the pH and using acid phosphatase as a model enzyme. The reversible photoacid G-acid functions as a proton donor, changing the pH rapidly and reversibly by using high power UV LEDs as an illumination source in our experimental setup. The reaction can be tightly controlled by simply switching the light on and off and should be applicable to a wide range of other enzymatic reactions, thus enabling miniaturization and parallelization through non-invasive optical means. Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-12685 SN - 2045-2322 VL - 9 ER - TY - JOUR A1 - Kober, Liane A1 - Schaefer, Paul A1 - Hollert, Henner A1 - Frohme, Marcus T1 - A novel strategy for high-throughput sample collection, analysis and visualization of explosives' concentrations for contaminated areas JF - International Journal of Environmental Science and Technology N2 - The use of explosives has led to a widespread distribution of 2,4,6-trinitrotoluene (TNT) and its by- and degradation products in the soil on former production and testing sites. The investigation of those large contaminated sites is so far based on a few selected soil samples, due to high costs of conventional HPLC and GC analysis, although huge differences in concentrations can already be found in small areas and different collection depths. We introduce a novel high-throughput screening system for those areas, which combines a smartphone-based collection of GPS data and soil characteristics with a fast MALDI-TOF MS quantification of explosives in soil sample extracts and finally a heatmap visualization of the explosives’ spread in soil and an analysis of correlation between concentrations and soil characteristics. The analysis of a 400 m2 area presented an extensive contamination with TNT and lower concentrations of the degradation and by-products aminodinitrotoluenes (ADNT) and dinitrotoluenes (DNT) next to a former production facility for TNT. The contamination decreased in deeper soil levels and depended on the soil type. Pure humus samples showed significantly lower contaminations compared to sand and humus/sand mixtures, which is likely to be caused by an increased binding potential of the humic material. No correlation was found between the vegetation and the concentration of explosives. Since the results were obtained and visualized within several hours, the MALDI-TOF MS based comprehensive screening and heatmap analysis might be valuable for a fast and high-throughput characterization of contaminated areas. KW - 2,4,6-trinitrotoluene KW - explosives KW - heatmap KW - MALDI-TOF MS KW - risk analysis KW - smartphone Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-15981 SN - 1735-2630 VL - 20 IS - 2 SP - 1399 EP - 1410 PB - Springer Nature ER - TY - JOUR A1 - Hornemann, Andrea A1 - Sinning, Denise A1 - Cortes, Sofia A1 - Campino, Lenea A1 - Emmer, Peggy A1 - Kuhls, Katrin A1 - Ulm, Gerhard A1 - Frohme, Marcus A1 - Beckhoff, Burkhard T1 - A pilot study on fingerprinting Leishmania species from the Old World using Fourier transform infrared spectroscopy JF - Analytical and Bioanalytical Chemistry N2 - Leishmania species are protozoan parasites and the causative agents of leishmaniasis, a vector borne disease that imposes a large health burden on individuals living mainly in tropical and subtropical regions. Different Leishmania species are responsible for the distinct clinical patterns, such as cutaneous, mucocutaneous, and visceral leishmaniasis, with the latter being potentially fatal if left untreated. For this reason, it is important to perform correct species identification and differentiation. Fourier transform infrared spectroscopy (FTIR) is an analytical spectroscopic technique increasingly being used as a potential tool for identification of microorganisms for diagnostic purposes. By employing mid-infrared (MIR) spectral data, it is not only possible to assess the chemical structures but also to achieve differentiation supported by multivariate statistic analysis. This work comprises a pilot study on differentiation of Leishmania species of the Old World (L. major, L. tropica, L. infantum, and L. donovani) as well as hybrids of distinct species by using vibrational spectroscopic fingerprints. Films of intact Leishmania parasites and their deoxyribonucleic acid (DNA) were characterized comparatively with respect to their biochemical nature and MIR spectral patterns. The strains’ hyperspectral datasets were multivariately examined by means of variance-based principal components analysis (PCA) and distance-based hierarchical cluster analysis (HCA). With the implementation of MIR spectral datasets we show that a phenotypic differentiation of Leishmania at species and intra-species level is feasible. Thus, FTIR spectroscopy can be further exploited for building up spectral databases of Leishmania parasites in view of high-throughput analysis of clinical specimens. KW - Fourier transform infrared spectroscopy KW - hierarchical cluster analysis (HCA) KW - principal components analysis (PCA) KW - Leishmania KW - DNA KW - multivariate differentiation Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-10080 SN - 1432-1130 ER - TY - JOUR A1 - Marcos-Zambrano, Laura Judith A1 - López-Molina, Víctor Manuel A1 - Bakir-Gungor, Burcu A1 - Frohme, Marcus A1 - Karaduzovic-Hadziabdic, Kanita A1 - Klammsteiner, Thomas A1 - Ibrahimi, Eliana A1 - Lahti, Leo A1 - Loncar-Turukalo, Tatjana A1 - Dhamo, Xhilda A1 - Simeon, Andrea A1 - Nechyporenko, Alina A1 - Pio, Gianvito A1 - Przymus, Piotr A1 - Sampri, Alexia A1 - Trajkovik, Vladimir A1 - Lacruz-Pleguezuelos, Blanca A1 - Aasmets, Oliver A1 - Araujo, Ricardo A1 - Anagnostopoulos, Ioannis A1 - Aydemir, Önder A1 - Berland, Magali A1 - Calle, M. Luz A1 - Ceci, Michelangelo A1 - Duman, Hatice A1 - Gündoğdu, Aycan A1 - Havulinna, Aki S. A1 - Kaka Bra, Kardokh Hama Najib A1 - Kalluci, Eglantina A1 - Karav, Sercan A1 - Lode, Daniel A1 - Lopes, Marta B. A1 - May, Patrick A1 - Nap, Bram A1 - Nedyalkova, Miroslava A1 - Paciência, Inês A1 - Pasic, Lejla A1 - Pujolassos, Meritxell A1 - Shigdel, Rajesh A1 - Susín, Antonio A1 - Thiele, Ines A1 - Truică, Ciprian-Octavian A1 - Wilmes, Paul A1 - Yilmaz, Ercument A1 - Yousef, Malik A1 - Claesson, Marcus Joakim A1 - Truu, Jaak A1 - Carrillo de Santa Pau, Enrique T1 - A toolbox of machine learning software to support microbiome analysis JF - Frontiers in Microbiology N2 - The human microbiome has become an area of intense research due to its potential impact on human health. However, the analysis and interpretation of this data have proven to be challenging due to its complexity and high dimensionality. Machine learning (ML) algorithms can process vast amounts of data to uncover informative patterns and relationships within the data, even with limited prior knowledge. Therefore, there has been a rapid growth in the development of software specifically designed for the analysis and interpretation of microbiome data using ML techniques. These software incorporate a wide range of ML algorithms for clustering, classification, regression, or feature selection, to identify microbial patterns and relationships within the data and generate predictive models. This rapid development with a constant need for new developments and integration of new features require efforts into compile, catalog and classify these tools to create infrastructures and services with easy, transparent, and trustable standards. Here we review the state-of-the-art for ML tools applied in human microbiome studies, performed as part of the COST Action ML4Microbiome activities. This scoping review focuses on ML based software and framework resources currently available for the analysis of microbiome data in humans. The aim is to support microbiologists and biomedical scientists to go deeper into specialized resources that integrate ML techniques and facilitate future benchmarking to create standards for the analysis of microbiome data. The software resources are organized based on the type of analysis they were developed for and the ML techniques they implement. A description of each software with examples of usage is provided including comments about pitfalls and lacks in the usage of software based on ML methods in relation to microbiome data that need to be considered by developers and users. This review represents an extensive compilation to date, offering valuable insights and guidance for researchers interested in leveraging ML approaches for microbiome analysis. KW - microbiome KW - machine learning KW - software KW - feature generation KW - feature analysis KW - data integration KW - microbial gene prediction KW - microbial metabolic modeling Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-18271 UR - https://www.frontiersin.org/articles/10.3389/fmicb.2023.1250806/ SN - 1664-302X VL - 14 PB - Frontiers ER - TY - JOUR A1 - D'Elia, Domenica A1 - Truu, Jaak A1 - Lahti, Leo A1 - Berland, Magali A1 - Papoutsoglou, Georgios A1 - Ceci, Michelangelo A1 - Zomer, Aldert A1 - Lopes, Marta B. A1 - Ibrahimi, Eliana A1 - Gruca, Aleksandra A1 - Nechyporenko, Alina A1 - Frohme, Marcus A1 - Klammsteiner, Thomas A1 - Carrillo de Santa Pau, Enrique A1 - Marcos-Zambrano, Laura Judith A1 - Hron, Karel A1 - Pio, Gianvito A1 - Simeon, Andrea A1 - Suharoschi, Ramona A1 - Moreno-Indias, Isabel A1 - Temko, Andriy A1 - Nedyalkova, Miroslava A1 - Apostol, Elena-Simona A1 - Truică, Ciprian-Octavian A1 - Shigdel, Rajesh A1 - Telalović, Jasminka Hasić A1 - Bongcam-Rudloff, Erik A1 - Przymus, Piotr A1 - Jordamović, Naida Babić A1 - Falquet, Laurent A1 - Tarazona, Sonia A1 - Sampri, Alexia A1 - Isola, Gaetano A1 - Pérez-Serrano, David A1 - Trajkovik, Vladimir A1 - Klucar, Lubos A1 - Loncar-Turukalo, Tatjana A1 - Havulinna, Aki S. A1 - Jansen, Christian A1 - Bertelsen, Randi J. A1 - Claesson, Marcus Joakim T1 - Advancing microbiome research with machine learning: key findings from the ML4Microbiome COST action JF - Frontiers in Microbiology N2 - The rapid development of machine learning (ML) techniques has opened up the data-dense field of microbiome research for novel therapeutic, diagnostic, and prognostic applications targeting a wide range of disorders, which could substantially improve healthcare practices in the era of precision medicine. However, several challenges must be addressed to exploit the benefits of ML in this field fully. In particular, there is a need to establish “gold standard” protocols for conducting ML analysis experiments and improve interactions between microbiome researchers and ML experts. The Machine Learning Techniques in Human Microbiome Studies (ML4Microbiome) COST Action CA18131 is a European network established in 2019 to promote collaboration between discovery-oriented microbiome researchers and data-driven ML experts to optimize and standardize ML approaches for microbiome analysis. This perspective paper presents the key achievements of ML4Microbiome, which include identifying predictive and discriminatory ‘omics’ features, improving repeatability and comparability, developing automation procedures, and defining priority areas for the novel development of ML methods targeting the microbiome. The insights gained from ML4Microbiome will help to maximize the potential of ML in microbiome research and pave the way for new and improved healthcare practices. KW - microbiome KW - machine learning KW - artificial intelligence KW - standard KW - best practice Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-18004 SN - 1664-302X VL - 14 PB - Frontiers ER - TY - JOUR A1 - Grebinyk, Anna A1 - Prylutska, Svitlana A1 - Grebinyk, Sergii A1 - Evstigneev, Maxim A1 - Krysiuk, Iryna A1 - Skaterna, Tetiana A1 - Horak, Iryna A1 - Sun, Yanfang A1 - Drobot, Liudmyla A1 - Matyshevska, Olga A1 - Prylutskyy, Yuriy A1 - Ritter, Uwe A1 - Frohme, Marcus T1 - Antitumor efficiency of the natural alkaloid berberine complexed with C60 fullerene in Lewis lung carcinoma in vitro and in vivo JF - Cancer Nanotechnology N2 - Background Berberine (Ber) is a herbal alkaloid with pharmacological activity in general and a high anticancer potency in particular. However, due to its low bioavailability, the difficulty in reaching a target and choosing the right dose, there is a need to improve approaches of Ber use in anticancer therapy. In this study, Ber, noncovalently bound to a carbon nanostructure C60 fullerene (C60) at various molar ratios of the components, was explored against Lewis lung carcinoma (LLC). Methods C60–Ber noncovalent nanocomplexes were synthesized in 1:2, 1:1 and 2:1 molar ratios. Ber release from the nanocomplexes was studied after prolonged incubation at different pH with the liquid chromatography–mass spectrometry analysis of free Ber content. Biological effects of the free and C60-complaxated Ber were studied in vitro towards LLC cells with phase-contrast and fluorescence microscopy, flow cytometry, MTT reduction, caspase activity and wound closure assays. The treatment with C60–Ber nanocomplex was evaluated in vivo with the LLC-tumored C57Bl mice. The mice body weight, tumor size, tumor weight and tumor weight index were assessed for four groups, treated with saline, 15 mg C60/kg, 7.5 mg Ber/kg or 2:1 C60-Ber nanocomplex (15 mg C60/kg, 7.5 mg Ber/kg). Results Ber release from C60–Ber nanocomplexes was promoted with medium acidification. LLC cells treatment with C60–Ber nanocomplexes was followed by enhanced Ber intracellular uptake as compared to free Ber. The cytotoxicity of the studied agents followed the order: free Ber < 1:2 < 1:1 < 2:1 C60–Ber nanocomplex. The potency of cytotoxic effect of 2:1 C60–Ber nanocomplex was confirmed by 21.3-fold decrease of IC50 value (0.8 ± 0.3 µM) compared to IC50 for free Ber (17 ± 2 µM). C60–Ber nanocomplexes induced caspase 3/7 activation and suppressed the migration activity of LLC cells. The therapeutic potency of 2:1 C60–Ber nanocomplex was confirmed in a mouse model of LLC. The tumor growth in the group treated with 2:1 C60–Ber nanocomplex is suppressed by approximately 50% at the end of experiment, while in the tumor-bearing group treated with free Ber no therapeutic effect was detected. Conclusions This study indicates that complexation of natural alkaloid Ber with C60 may be a novel therapeutic strategy against lung carcinoma. Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-14749 SN - 1868-6966 VL - 12 SP - 24 PB - BioMed Central ER - TY - JOUR A1 - Gossing, Wilhelm A1 - Frohme, Marcus A1 - Radke, Lars T1 - Biomarkers for Liquid Biopsies of Pituitary Neuroendocrine Tumors JF - Biomedicines N2 - Pituitary neuroendocrine tumors (PitNET) do not only belong to the most common intracranial neoplasms but seem to be generally more common than has been thought. Minimally invasive liquid biopsies have the potential to improve their early screening efficiency as well as monitor prognosis by facilitating the diagnostic procedures. This review aims to assess the potential of using liquid biopsies of different kinds of biomarker species that have only been obtained from solid pituitary tissues so far. Numerous molecules have been associated with the development of a PitNET, suggesting that it often develops from the cumulative effects of many smaller genetic or epigenetic changes. These minor changes eventually pile up to switch critical molecules into tumor-promoting states, which may be the key regulatory nodes representing the most potent marker substances for a diagnostic test. Drugs targeting these nodes may be superior for the therapeutic outcome and therefore the identification of such pituitary-specific cellular key nodes will help to accelerate their application in medicine. The ongoing genetic degeneration in pituitary adenomas suggests that repeated tumor profiling via liquid biopsies will be necessary for personalized and effective treatment solutions. Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-13307 SN - 2227-9059 VL - 8 IS - 6 ER - TY - JOUR A1 - Grebinyk, Anna A1 - Grebinyk, Sergii A1 - Prylutska, Svitlana A1 - Ritter, Uwe A1 - Matyshevska, Olga A1 - Dandekar, Thomas A1 - Frohme, Marcus T1 - C60 fullerene accumulation in human leukemic cells and perspectives of LED-mediated photodynamic therapy JF - Free Radical Biology and Medicine N2 - Recent progress in nanobiotechnology has attracted interest to a biomedical application of the carbon nanostructure C60 fullerene since it possesses a unique structure and versatile biological activity. C60 fullerene potential application in the frame of cancer photodynamic therapy (PDT) relies on rapid development of new light sources as well as on better understanding of the fullerene interaction with cells. The aim of this study was to analyze C60 fullerene effects on human leukemic cells (CCRF-CEM) in combination with high power single chip light-emitting diodes (LEDs) light irradiation of different wavelengths: ultraviolet (UV, 365 nm), violet (405 nm), green (515 nm) and red (632 nm). The time-dependent accumulation of fullerene C60 in CCRF-CEM cells up to 250 ng/106 cells at 24 h with predominant localization within mitochondria was demonstrated with immunocytochemical staining and liquid chromatography mass spectrometry. In a cell viability assay we studied photoexcitation of the accumulated C60 nanostructures with ultraviolet or violet LEDs and could prove that significant phototoxic effects did arise. A less pronounced C60 fullerene phototoxic effect was observed after irradiation with green, and no effect was detected with red light. A C60 fullerene photoactivation with violet light induced substantial ROS generation and apoptotic cell death, confirmed by caspase3/7 activation and plasma membrane phosphatidylserine externalization. Our work proved C60 fullerene ability to induce apoptosis of leukemic cells after photoexcitation with high power single chip 405 nm LED as a light source. This underlined the potential for application of C60 nanostructure as a photosensitizer for anticancer therapy. Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-10588 SN - 1873-4596 VL - 124 SP - 319 EP - 327 ER -