Search results for "DISCOVERY"
showing 10 items of 4119 documents
1-ethyl-3-(6-methylphenanthridine-8-il) urea modulates TLR3/9 activation and induces selective pro-inflammatory cytokine expression in vitro.
2017
We have previously demonstrated the nucleic acid binding capacity of phenanthridine derivatives (PHTs). Because nucleic acids are potent inducers of innate immune response through Toll-like receptors (TLRs), and because PTHs bear a structural resemblance to commonly used synthetic ligands for TLR7/8, we hypothesized that PHTs could modulate/activate immune response. We found that compound M199 induces secretion of IL-6, IL-8 and TNFα in human PBMCs and inhibits TLR3/9 activation in different cellular systems (PBMCs, HEK293 and THP-1 cell lines).
Introduction: Novel hybrid combinations containing synthetic or antibiotic drugs with plant-derived phenolic or terpenoid compounds
2017
Abstract Background There is a paradigm shift in chemotherapy from mono-drug therapy towards multidrug combination regimens. Natural products from medicinal plants may play an important role for the design of novel combination therapy protocols. Hypothesis We introduce the novel term “hybrid combination” for the therapeutic combination of chemically defined plant-derived constituents (e.g. phenolic or terpenoid compounds with synthetic or antibiotic drugs to increase pharmacological activity and simultaneously toxic side effects. Study design Several literature databases were screened on the combination of phenolic/terpenoid compounds with synthetic/antibiotic drugs. Results Phenolic compou…
Cancer combination therapy of the sesquiterpenoid artesunate and the selective EGFR-tyrosine kinase inhibitor erlotinib.
2017
Abstract Background The shift from cytotoxic to targeted chemotherapy led to improved treatment outcomes in oncology. Nevertheless, many cancer patients cannot be cured from their disease because of the development of drug resistance and side effects. Purpose There is an ongoing quest for novel compounds, which raised not only the interest in natural products but also in novel combination therapy regimens. Study design In this review, we report on the inhibition epidermal growth factor receptor (EGFR) by targeted small molecules and their combination with natural products from medicinal plants. Results The combination of erlotinib with artesunate leads to synergistic inhibition of cell grow…
Large-scale identification of functional microRNA targeting reveals cooperative regulation of the hemostatic system.
2018
Essentials MicroRNAs (miRNAs) regulate the molecular networks controlling biological functions such as hemostasis. We utilized novel methods to analyze miRNA-mediated regulation of the hemostatic system. 52 specific miRNA interactions with 11 key hemostatic associated genes were identified. Functionality and drugability of miRNA-19b-3p against antithrombin were demonstrated in vivo. SUMMARY: Background microRNAs (miRNAs) confer robustness to complex molecular networks regulating biological functions. However, despite the involvement of miRNAs in almost all biological processes, and the importance of the hemostatic system for a multitude of actions in and beyond blood coagulation, the role o…
Recent discoveries of anticancer flavonoids.
2017
Abstract In this review we report the recent advances in anticancer activity of the family of natural occurring flavonoids, covering the time span of the last five years. The bibliographic data will be grouped, on the basis of biological information, in two great categories: reports in which the extract plants bioactivity is reported and the identification of each flavonoid is present or not, and reports in which the anticancer activity is attributable to purified and identified flavonoids from plants. Wherever possible, the targets and mechanisms of action as well as the structure-activity relationships of the molecules will be reported. Also, in the review it was thoroughly investigated t…
All-atom simulations to studying metallodrugs/target interactions.
2021
Abstract Metallodrugs are extensively used to treat and diagnose distinct disease types. The unique physical–chemical properties of metal ions offer tantalizing opportunities to tailor effective scaffolds for selectively targeting specific biomolecules. Modern experimental techniques have collected a large body of structural data concerning the interactions of metallodrugs with their biomolecular targets, although being unable to exhaustively assess the molecular basis of their mechanism of action. In this scenario, the complementary use of accurate computational methods allows uncovering the minutiae of metallodrugs/targets interactions and their underlying mechanism of action at an atomic…
Next-generation sequencing: big data meets high performance computing
2017
The progress of next-generation sequencing has a major impact on medical and genomic research. This high-throughput technology can now produce billions of short DNA or RNA fragments in excess of a few terabytes of data in a single run. This leads to massive datasets used by a wide range of applications including personalized cancer treatment and precision medicine. In addition to the hugely increased throughput, the cost of using high-throughput technologies has been dramatically decreasing. A low sequencing cost of around US$1000 per genome has now rendered large population-scale projects feasible. However, to make effective use of the produced data, the design of big data algorithms and t…
Improving Docking Performance Using Negative Image-Based Rescoring
2017
Despite the large computational costs of molecular docking, the default scoring functions are often unable to recognize the active hits from the inactive molecules in large-scale virtual screening experiments. Thus, even though a correct binding pose might be sampled during the docking, the active compound or its biologically relevant pose is not necessarily given high enough score to arouse the attention. Various rescoring and post-processing approaches have emerged for improving the docking performance. Here, it is shown that the very early enrichment (number of actives scored higher than 1% of the highest ranked decoys) can be improved on average 2.5-fold or even 8.7-fold by comparing th…
The good and bad of targeting cancer-associated extracellular matrix
2017
The maintenance of tissue homeostasis requires extracellular matrix (ECM) remodeling. Immune cells actively participate in regenerating damaged tissues contributing to ECM deposition and shaping. Dysregulated ECM deposition characterizes fibrotic diseases and cancer stromatogenesis, where a chronic inflammatory state sustains the ECM increase. In cancer, the ECM fosters several steps of tumor progression, providing pro-survival and proliferative signals, promoting tumor cell dissemination via collagen fibers or acting as a barrier to impede drug diffusion. Interfering with processes leading to chronic ECM deposition, as occurring in cancer, might allow the simultaneous targeting of both pri…
Attitudes and beliefs on influenza vaccination during the covid-19 pandemic: Results from a representative italian survey
2020
The last 2019/20 northern hemisphere influenza season overlapped with the first wave of coronavirus disease 2019 (COVID-19) pandemic. Italy was the first western country where severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread to a significant extent. In this representative cross-sectional survey, we aimed to describe some opinions and attitudes of the Italian general population towards both influenza vaccination and the COVID-19 pandemic, and to identify potential modifiers of the decision-making process regarding the uptake of the 2020/21 influenza vaccine. A total of 2543 responses were analyzed. Although most (74.8%) participants valued influenza vaccination positively …