A data structure for protein-ligand morphological matching

Pattern recognition techniques can be applied very profitably to proteomics because of the strong linkage of the protein’s molecule morphology and proteins functionalities. In fact, geometric and topological congruence (concavity and convexity correspondences) can be often considered certainly not sufficient but in many cases necessary conditions. In this connection, considering that the “active sites” are always located in one of the biggest concavities (in one of the largest “pockets”) and that the ligand must match this concavity, its effective part must be mainly convex. For this reason, the matching potential can be evaluated through an Extended Gaussian Image (EGI) shape representation. The original EGI, and a few extensions (namely Complex EGI and Enriched Complex EGI) representations and their correspondent concrete data-structures are here discussed. This data structure is then exploited for the implementation and evaluation of the matching stance between the small ligand molecule and a pocket of a protein macromolecule

The State-of-the-Art of Phase II/III Clinical Trials for Targeted Pancreatic Cancer Therapies

Pancreatic cancer is a devastating disease with very poor prognosis. Currently, surgery followed by adjuvant chemotherapy represents the only curative option which, unfortunately, is only available for a small group of patients. The majority of pancreatic cancer cases are diagnosed at advanced or metastatic stage when surgical resection is not possible and treatment options are limited. Thus, novel and more effective therapeutic strategies are urgently needed. Molecular profiling together with targeted therapies against key hallmarks of pancreatic cancer appear as a promising approach that could overcome the limitations of conventional chemo- and radio-therapy. In this review, we focus on the latest personalised and multimodal targeted therapies currently undergoing phase II or III clinical trials. We discuss the most promising findings of agents targeting surface receptors, angiogenesis, DNA damage and cell cycle arrest, key signalling pathways, immunotherapies, and the tumour microenvironment

The fate of bacteria in urban wastewater-irrigated peach tree: a seasonal evaluation from soil to canopy

Irrigation with wastewater can be a solution to preserve and mitigate freshwater demand, in particular during drought periods. Unfortunately, wastewater, although being treated at different levels, could be a carrier of human pathogens (e.g., E. coli) and potentially contaminate crops for human consumptions.This study investigated the seasonal microbiological concentrations, on soil, shoot and fruit tissues of potted peach trees, following two irrigation treatments: freshwater (FW) and secondary urban wastewater without the final disinfection treatment (SW). E. coli was only detected in SW irrigated soil, whereas total coliforms (TC) and total bacteria counts (TBC) were similar in both treatments throughout the season. EndophyticE. coli, Salmonella spp. and TC were not detected in shoot and fruit, but a higher presence of total bacteria (TBC) was observed in SW-irrigated tree compared to FWirrigated tree. In particular, SW shoots had a higher load compared to fruits, thus showing a potential effect of leaf transpiration, that promoted the transfer of water-borne bacteria from soil to the epigeal part (shoot). The adoption of low-quality SW (even above the microbiological limits of the European Regulation 2020/741 for wastewater re-use in agriculture), when a drip irrigation method is applied, could be a valid alternative to save fresh water without compromising fruit safety

Proteomics as a quality control tool of pharmaceutical probiotic bacterial lysate products

Probiotic bacteria have a wide range of applications in veterinary and human therapeutics. Inactivated probiotics are complex samples and quality control (QC) should measure as many molecular features as possible. Capillary electrophoresis coupled to mass spectrometry (CE/MS) has been used as a multidimensional and high throughput method for the identification and validation of biomarkers of disease in complex biological samples such as biofluids. In this study we evaluate the suitability of CE/MS to measure the consistency of different lots of the probiotic formulation Pro-Symbioflor which is a bacterial lysate of heat-inactivated Escherichia coli and Enterococcus faecalis. Over 5000 peptides were detected by CE/MS in 5 different lots of the bacterial lysate and in a sample of culture medium. 71 to 75% of the total peptide content was identical in all lots. This percentage increased to 87–89% when allowing the absence of a peptide in one of the 5 samples. These results, based on over 2000 peptides, suggest high similarity of the 5 different lots. Sequence analysis identified peptides of both E. coli and E. faecalis and peptides originating from the culture medium, thus confirming the presence of the strains in the formulation. Ontology analysis suggested that the majority of the peptides identified for E. coli originated from the cell membrane or the fimbrium, while peptides identified for E. faecalis were enriched for peptides originating from the cytoplasm. The bacterial lysate peptides as a whole are recognised as highly conserved molecular patterns by the innate immune system as microbe associated molecular pattern (MAMP). Sequence analysis also identified the presence of soybean, yeast and casein protein fragments that are part of the formulation of the culture medium. In conclusion CE/MS seems an appropriate QC tool to analyze complex biological products such as inactivated probiotic formulations and allows determining the similarity between lots