Several new cyano-substituted derivatives with pyrrolo[1,2-a]quinoline and pyrrolo[2,1-a]isoquinoline scaffolds were synthesized by the [3 + 2] cycloaddition of (iso)quinolinium ylides to fumaronitrile. The cycloimmonium ylides reacted in situ as 1,3-dipoles with fumaronitrile to selectively form distinct final compounds, depending on the structure of the (iso)quinolinium salt. Eleven compounds were evaluated for their anticancer activity against a panel of 60 human cancer cell lines. The most potent compound 9a showed a broad spectrum of antiproliferative activity against cancer cell lines representing leukemia, melanoma and cancer of lung, colon, central nervous system, ovary, kidney, breast and prostate cancer. In vitro assays and molecular docking revealed tubulin interaction properties of compound 9a.

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Regenerative medicine is challenged by the need to conform to rigorous guidelines for establishing safe and effective development and translation of stem cell-based therapies. Counteracting widespread concerns regarding unproven cell therapies, stringent cell-based assays seek not only to avoid harm but also to enhance quality and efficacy. Potency indicates that the cells are functionally fit for purpose before they are administered to the patient. It is a paramount quantitative critical quality attribute serving as a decisive release criterion. Given a broad range of stem cell types and therapeutic contexts the potency assay often comprises one of the most demanding hurdles for release of a cell therapy medicinal product. With need for improved biomarker assessment and expedited measurement, recent advances in graphene-based biosensors suggest that they are poised to be valuable platforms for accelerating potency assay development. Among several potential advantages, they offer versatility for sensitive measurement of a broad range of potential biomarker types, cell biocompatibility for direct measurement, and small sample sufficiency, plus ease of use and point-of-care applicability.

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IntroductionThe intestinal microbiota is vital to human health, and has a profound influence on several biological processes including inflammation and pathogen resistance. Antibiotic intake greatly impacts bacterial diversity, can increase antibiotic resistance and impair the equilibrium between bacterial species. The key to grasping post-antibiotic effects on the gut microbiota rests on the implementation of a suitable procedure to isolate microbial DNA and a meticulous consideration of experimental sequencing artefacts.MethodsWe herein report the bacterial community dynamics of a cohort of 128 surgical oncology patients before and after the intravenous administration of cefuroxime, an antibiotic routinely used in surgical antibioprophylaxis with proven efficiency against both gram-positive and gram-negative bacteria. In our study, we analyzed patient fecal samples collected through rectal examination before and 7 days post cefuroxime treatment by employing a high-throughput sequencing assay which targets the V3–V4 region of the 16S rRNA gene. A first challenge in applying the study design was to extract an appropriate amount of DNA characteristic to the sampled microbiota, which implied the use of both mechanical (ceramic beads) and chemical (proteinase K, lysozyme and lysostaphin) lysis.ResultsGut microbiota richness and composition was significantly different between the two groups, but most differences were determined by additional perioperative procedures, rather than antibioprophylaxis. Intestinal microbiota composition was not significantly changed one week post cefuroxime treatment when compared to pre-treatment condition for patients without mechanical bowel preparation, but some loss in taxonomic variety could be observed.DiscussionTaken together, cefuroxime does not promote short-term dysbiosis in surgical patients without any additional perioperative procedures.