Project description:Plant alkaloids represent a diverse group of nitrogen-containing natural products. These compounds are considered valuable in drug discovery and development. High-throughput identification of such plant secondary metabolites in complex plant extracts is essential for drug discovery, lead optimization, and understanding the biological pathway. The present study aims to rapidly identify different classes of alkaloids in plant extracts through the liquid chromatography with electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) approach using 161 isolated and purified alkaloids. These are biologically important unique alkaloids belonging to different sub-classes such as isoquinoline, quinoline, indole, tropane, pyridine, piperidine, quinolizidine, aporphine, steroidal, and terpenoid. The majority of these are not available commercially and are known to manifest valuable biological activities. Four pools of a maximum of 50 phytostandards each were prepared, based on their log <i>P</i> value to minimize co-elution for rapid and cost-effective analyses. MS/MS spectra were acquired in the positive ionization mode by using their [M + H]<sup>+</sup> and/or [M + Na]<sup>+</sup> with both the average collisional energy (25.5-62 eV) and individual collisional energies (10, 20, 30, and 40 eV). Accurate mass, high-resolution mass spectrometry (HR-MS) data, MS/MS data, and retention times were curated for each compound. The developed LC-MS/MS method was successfully used to interrogate and fast dereplicate alkaloids in 13 medicinal plant extracts and a herbal formulation. A total of 56 alkaloids were identified based on the reference standard retention times (RTs), HR-MS spectra, and/or MS/MS spectra. The MS data have been submitted to the MetaboLights online database (MTBLS2914). The mass spectrometric and chromatographic data will be useful for the discovery of new congeners and the study of biological pathways of alkaloids in the plant kingdom.
Project description:We report the human homologous microRNA profiles in food-grade, bovine-sourced sirloin, heart and adrenal tissue (raw, cooked, and laboratory-prepared pasteurized, freeze-dried extracts)
Project description:Antibody–drug conjugates (ADCs) are a powerful class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. In this study, we developed novel dual-payload ADC (DualADC) platforms that enable co-delivery of a chemotherapeutic agent for direct tumor cell killing and a toll-like receptor agonist to stimulate antitumor immunity. Using triple-negative breast cancer (TNBC) as a model, we established advanced cysteine/lysine co-conjugation strategies optimized for antibody–drug ratio (ADR) and drug–drug ratio (DDR). These refinements minimized hydrophobicity-induced precipitation, enhanced conjugation efficiency, and improved formulation stability. In vivo evaluations in two xenograft mouse models demonstrated strong antitumor efficacy, highlighting the therapeutic potential of DualADCs as a next-generation approach for synergistic chemo-immunotherapy.
Project description:Dichloromethane (DCM) extracts of aerial parts and roots of Waltheria indica analyzed in UHPLC-MS/MS in positive ionization mode. .raw, .mzML and MzMine2 processed files(spectra .mgf and feature table .csv) are available.
References:
Cretton, Sylvian, Stéphane Dorsaz, Antonio Azzollini, Quentin Favre-Godal, Laurence Marcourt, Samad Nejad Ebrahimi, Francine Voinesco, et al. 2016. “Antifungal Quinoline Alkaloids from Waltheria Indica.” Journal of Natural Products 79 (2): 300–307.
Cretton, S., L. Breant, L. Pourrez, C. Ambuehl, L. Marcourt, S. N. Ebrahimi, M. Hamburger, et al. 2014. “Antitrypanosomal Quinoline Alkaloids from the Roots of Waltheria Indica.” Journal of Natural Products 77 (10): 2304–11.
Project description:We used phytochemical profiling techniques to generate a list of compounds present in each of 13 Equisetum arvense samples sourced globally. We used microarrays to detail the global programme of gene expression underlying the treatment of the model system Saccharomyces cerevisiae to a chosen number of these extracts. A thorough bioinformatic analysis was performed to identify the relationship between phytochemical and gene expression response profiles.
Project description:Abraxane, a nanoparticle (NP) formulation of paclitaxel (PTX), has been demonstrated to be more effective than Taxol, the small molecule formulation, for the treatment of breast cancer and non-small cell lung cancer (NSCLC). It was reported that Abraxane existed in plasma as particles with the size of ~10 nm. NPs get in and out of the cells by endocytosis and exocytosis, whereas small molecules by diffusion and efflux. It is intriguing to know whether the improved pharmaceutical performance is related to the “too-big-to-be-pumped-out” phenomenon. Here we established an Abraxane-resistant NSCLC cell line A549/Abr and compared its transcriptomes with that of the Abraxane-sensitive parental cell line by RNA-Seq technology. To our surprise, the most significantly up-regulated genes were ABC transporters, the common efflux pump for small molecules. We further found that the ABCB1 inhibitor Verapamil reversed the drug resistance and confirmed the important role of ABCB1 in Abraxane resistance.