An evaluation of the usability of argon plasma-treated bacterial cellulose as a carrier for controlled releases of glycoside hydrolases PelAhPelA_{h} and PslGhPslG_{h}, which are able to eradicate biofilm

Bacterial cellulose is a unique biopolymer that has found numerous biomedical applications, such as being an excellent wound-dressing material or a carrier for delivering active compounds. The purpose of this study was to analyze the ability of modified bacterial cellulose (BC) using low-pressure Ar plasma to control the release of glycoside hydrolases with antibiofilm activity, namely $PelA_{h}$ and $PslG_{h}$, from Pseudomonas aeruginosa. The chemical composition and morphology of the BC surfaces were characterized using photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The analyses revealed significant changes in the chemical composition of the BC surface due to the introduction of charged functional groups and the conversion of its well-ordered structure into a more amorphous form. The release profiles of enzymes from both forms of the carrier were different and depended on their structural properties. However, a significant impact of BC modification on protein release behavior from the carrier was observed only for $PslG_{h}$. Both enzymes, when immobilized on pristine and argon plasma-modified BC, retained their ability to effectively reduce biofilm levels, similarly to their soluble form. Ar plasma-modified BC with immobilized specific hydrolases can be used as an effective tool for inhibiting P. aeruginosa biofilm development

Przewoźna maszyna wyciągowa B-1200/M/AC-2m/s – mobilność bez ograniczeń

W artykule zaprezentowano przewoźną maszynę wyciągową B-1200/M/AC-2m/s, produkcji MWM Elektro Sp. z o. o., umożliwiającą szybkie i swobodne jej przemieszczanie między obsługiwanymi szybami. Przedstawiono opis techniczny maszyny wyciągowej, jak i wymagania przepisów ruchu drogowego, z którymi musieli się zmierzyć konstruktorzy przewoźnej maszyny wyciągowej podczas jej projektowania

Different Regulation of Interleukin-1 Production and Activity in Monocytes and Macrophages: Innate Memory as an Endogenous Mechanism of IL-1 Inhibition

Production and activity of interleukin (IL)-1β are kept under strict control in our body, because of its powerful inflammation-promoting capacity. Control of IL-1β production and activity allows IL-1 to exert its defensive activities without causing extensive tissue damage. Monocytes are the major producers of IL-1β during inflammation, but they are also able to produce significant amounts of IL-1 inhibitors such as IL-1Ra and the soluble form of the decoy receptor IL-1R2, in an auto-regulatory feedback loop. Here, we investigated how innate immune memory could modulate production and activity of IL-1β by human primary monocytes and monocyte-derived tissue-like/deactivated macrophages in vitro. Cells were exposed to Gram-negative (Escherichia coli) and Gram-positive (Lactobacillus acidophilus) bacteria for 24 h, then allowed to rest, and then re-challenged with the same stimuli. The presence of biologically active IL-1β in cell supernatants was calculated as the ratio between free IL-1β (i.e., the cytokine that is not bound/inhibited by sIL-1R2) and its receptor antagonist IL-1Ra. As expected, we observed that the responsiveness of tissue-like/deactivated macrophages to bacterial stimuli was lower than that of monocytes. After resting and re-stimulation, a memory effect was evident for the production of inflammatory cytokines, whereas production of alarm signals (chemokines) was minimally affected. We observed a high variability in the innate memory response among individual donors. This is expected since innate memory largely depends on the previous history of exposure or infections, which is different in different subjects. Overall, innate memory appeared to limit the amount of active IL-1β produced by macrophages in response to a bacterial challenge, while enhancing the responsiveness of monocytes. The functional re-programming of mononuclear phagocytes through modulation of innate memory may provide innovative approaches in the management of inflammatory diseases, as well as in the design of new immunization strategies. In this respect, the interindividual variability in innate memory suggests the need of a personalized assessment

Discovery of inhibitory fragments that selectively target Spire2−FMN2 interaction

Here, we report the fragment-based drug discovery of potent and selective fragments that disrupt the Spire2–FMN2 but not the Spire1–FMN2 interaction. Hit fragments were identified in a differential scanning fluorimetry-based screen of an in-house library of 755 compounds and subsequently validated in multiple orthogonal biophysical assays, including fluorescence polarization, microscale thermophoresis, and 1H–15N HSQC nuclear magnetic resonance. Extensive structure–activity relationships combined with molecular docking followed by chemical optimization led to the discovery of compound 13, which exhibits micromolar potency and high ligand efficiency (LE = 0.38). Therefore, this fragment represents a validated starting point for the future development of selective chemical probes targeting the Spire2–FMN2 interaction

Surgical treatment of rectal cancer in Poland — a report from a prospective, multi-centre observational study PSSO_01 conducted under the auspices of the Polish Society of Surgical Oncology

Introduction. Since 2016, as part of the PSSO_01 multi-centre research project conducted under the auspices of the Polish Society of Surgical Oncology, clinical data on rectal cancer treatment have been collected. The objective of the study was to illustrate the state of early results of surgical treatment. Material and methods. The research project is multi-centre in nature. Data shall be collected electronically. The study protocol does not impose or suggest any course of procedure. It only systematizes the way data are collected for scientific purposes. The analysis of early results of surgical treatment was compared with the results of population studies from other European countries (Netherlands, Belgium). Results. By the end of June 2018, 736 patients were registered in the study. In 399 (54.2%) an anterior resection was performed. More than half of patients undergoing subsequent surgical treatment (54.2%) receive neoadjuvant treatment, with the percentage of patients undergoing radiotherapy or radiochemical treatment for lower rectal cancer being about 70%. Most patients (96%) are operated in elective procedure. The percentage of laparoscopic surgeries is low (8.6%). Postoperative complications are observed in 21.1% of patients. Severe complications (grades III–V according to Clavien-Dindo classification) occur in 7.6% of patients undergoing surgery. Postoperative mortality is 1.1%. Discussion. Although the project does not have the character of a registry and does not allow for drawing wider conclusions concerning the compliance with the standards of qualification for neoadjuvant treatment, the important information is that more than half of rectal cancer patients receive preoperative treatment, and the percentage of severe postoperative complications does not exceed 10%. Conclusions. The results of the PSSO_01 project are representative and reflect the actual situation concerning surgical treatment of rectal cancer patients in Poland