Analgesic activity of new complex compounds SnCl4 with salicyloylhydrazones of benzaldehyde and brombenzaldehyde

The physiological role of pain helps to avoid or limit the tissue damage and therefore it provides the vital protective function. It has been previously studied, that complex compounds SnCl4 with salicyloylhydrazones of benzaldehyde and brombenzaldehyde as well as their components represent the practical interest by the manifestation of anti-inflammatory and antidepressive action. In this case the analgesic properties of the complexes themselves, as well as compounds belonging to their structure were of interest of our study. The experiments were performed on white mice. Several chemical (allyl isothiocyanate or AITC, capsaicin, formalin) and thermal effects have been chosen in this investigation for studying the analgesic activity and establishing the possible mechanisms of antinociceptive effect. The tested compounds showed a mixed type of receptor interaction using models with different types of stimulation, which allows to make conclusions about their perspective as highly effective analgesics with a complex mechanism of action

Analgesic activity of new complex compounds SnCl4 with salicyloylhydrazones of benzaldehyde and brombenzaldehyde

The physiological role of pain helps to avoid or limit the tissue damage and therefore it provides the vital protective function. It has been previously studied, that complex compounds SnCl4 with salicyloylhydrazones of benzaldehyde and brombenzaldehyde as well as their components represent the practical interest by the manifestation of anti-inflammatory and antidepressive action. In this case the analgesic properties of the complexes themselves, as well as compounds belonging to their structure were of interest of our study. The experiments were performed on white mice. Several chemical (allyl isothiocyanate or AITC, capsaicin, formalin) and thermal effects have been chosen in this investigation for studying the analgesic activity and establishing the possible mechanisms of antinociceptive effect. The tested compounds showed a mixed type of receptor interaction using models with different types of stimulation, which allows to make conclusions about their perspective as highly effective analgesics with a complex mechanism of action

Panel 3. World-wide experiences

Brazilian women in audio description: 20 years of history / Lucinéa Marcelino Villela (Universidade Estadual Paulista) ; Audio describing foreign animation films into Greek / Ismini Karantzi (Ionian University) ; The description of crime films: a reception study / Evangelia Likaou (Ionian University) ; The Verouvindo film festival experience: shaping assessment criteria for best audio description / Eliana Franco (Sintagma Lda), Liliana Tavares (COM Acessibilidade Comunicacional) ; Volunteer accessibility services in Russia / Elena Aleksandrova (Alba Multimedia LLC) ; Audio description on Polish commercial television: first experiences and next steps / Agnieszka Walczak (ViacomCBS Networks International), Alexandra Dobrowolska (ViacomCBS Networks International). Chair: Veronika Rot (RTVSLO)Audio description on Polish commercial television: first experiences and next steps / Agnieszka Walczak (ViacomCBS Networks International), Alexandra Dobrowolska (ViacomCBS Networks International). This video presentation is not available in open access. Only the abstract is available

Platinum mineralization comparative characteristics of the some Far East deposits

In this article shown platinum mineralization comparative characteristics for three deposits: Kondoer-traditional unique deposit and other two probably alternative source of platinum: the Poperechnoe ironmanganese deposit and the Malmyzh copper-porphyry deposit. Platinoids of the Kondoer deposit are the chain Pt>>Ir>Os>Ru=Rh>Pd. The presences of platinum crystals are characteristic, there are over 50 rare and new platinoids minerals in different combinations. There are gold and silver. Platinoids from the iron-manganese ore of Poperechnoe are as Pt>>Rh≈Ir>Ru≈Os>Pd. A scattered dissemination of arsenide sulfate and sulfides of Rh, Ir, Ru, Os are noted in the platinum. Palladium is present as impurities in gold and platinum. The gold content is different-with admixtures Ag, Pb, Cd, Fe. At this stage the platinoids content in oxidized ores of the Malmyzh gold-copper porphyry deposit is Pt ≈ Pd. The gold is present as electrum. There is native silver cadmium

Platinum mineralization comparative characteristics of the some Far East deposits

In this article shown platinum mineralization comparative characteristics for three deposits: Kondoer-traditional unique deposit and other two probably alternative source of platinum: the Poperechnoe ironmanganese deposit and the Malmyzh copper-porphyry deposit. Platinoids of the Kondoer deposit are the chain Pt>>Ir>Os>Ru=Rh>Pd. The presences of platinum crystals are characteristic, there are over 50 rare and new platinoids minerals in different combinations. There are gold and silver. Platinoids from the iron-manganese ore of Poperechnoe are as Pt>>Rh≈Ir>Ru≈Os>Pd. A scattered dissemination of arsenide sulfate and sulfides of Rh, Ir, Ru, Os are noted in the platinum. Palladium is present as impurities in gold and platinum. The gold content is different-with admixtures Ag, Pb, Cd, Fe. At this stage the platinoids content in oxidized ores of the Malmyzh gold-copper porphyry deposit is Pt ≈ Pd. The gold is present as electrum. There is native silver cadmium

Resilient microorganisms in dust samples of the International Space Station—survival of the adaptation specialists

Background: The International Space Station (ISS) represents a unique biotope for the human crew but also for introduced microorganisms. Microbes experience selective pressures such as microgravity, desiccation, poor nutrient-availability due to cleaning, and an increased radiation level. We hypothesized that the microbial community inside the ISS is modified by adapting to these stresses. For this reason, we analyzed 8-12 years old dust samples from Russian ISS modules with major focus on the long-time surviving portion of the microbial community. We consequently assessed the cultivable microbiota of these samples in order to analyze their extremotolerant potential against desiccation, heat-shock, and clinically relevant antibiotics. In addition, we studied the bacterial and archaeal communities from the stored Russian dust samples via molecular methods (next-generation sequencing, NGS) and compared our new data with previously derived information from the US American ISS dust microbiome. Results: We cultivated and identified in total 85 bacterial, non-pathogenic isolates (17 different species) and 1 fungal isolate from the 8-12 year old dust samples collected in the Russian segment of the ISS. Most of these isolates exhibited robust resistance against heat-shock and clinically relevant antibiotics. Microbial 16S rRNA gene and archaeal 16S rRNA gene targeting Next Generation Sequencing showed signatures of human-associated microorganisms (Corynebacterium, Staphylococcus, Coprococcus etc.), but also specifically adapted extremotolerant microorganisms. Besides bacteria, the detection of archaeal signatures in higher abundance was striking. Conclusions: Our findings reveal (i) the occurrence of living, hardy microorganisms in archived Russian ISS dust samples, (ii) a profound resistance capacity of ISS microorganisms against environmental stresses, and (iii) the presence of archaeal signatures on board. In addition, we found indications that the microbial community in the Russian segment dust samples was different to recently reported US American ISS microbiota

Outside Mainstream Electronic Databases: Review of Studies Conducted in the USSR and Post-Soviet Countries on Electric Current-Assisted Consolidation of Powder Materials

This paper reviews research articles published in the former USSR and post-soviet countries on the consolidation of powder materials using electric current that passes through the powder sample and/or a conductive die-punch set-up. Having been published in Russian, many of the reviewed papers are not included in the mainstream electronic databases of the scientific articles and thus are not known to the scientific community. The present review is aimed at filling this information gap. In the paper, the electric current-assisted sintering techniques based on high- and low-voltage approaches are presented. The main results of the theoretical modeling of the processes of electromagnetic field-assisted consolidation of powder materials are discussed. Sintering experiments and related equipment are described and the major experimental results are analyzed. Sintering conditions required to achieve the desired properties of the sintered materials are provided for selected material systems. Tooling materials used in the electric current-assisted consolidation set-ups are also described

Additional file 5: Table S4. of Resilient microorganisms in dust samples of the International Space Station—survival of the adaptation specialists

DADA2 output (archaeal primer set; negative controls removed). (XLSX 8 kb

GMP-Compliant Manufacturing of TRUCKs: CAR T Cells targeting GD2 and Releasing Inducible IL-18

Chimeric antigen receptor (CAR)-engineered T cells can be highly effective in the treatment of hematological malignancies, but mostly fail in the treatment of solid tumors. Thus, approaches using 4th advanced CAR T cells secreting immunomodulatory cytokines upon CAR signaling, known as TRUCKs (“T cells redirected for universal cytokine-mediated killing”), are currently under investigation. Based on our previous development and validation of automated and closed processing for GMP-compliant manufacturing of CAR T cells, we here present the proof of feasibility for translation of this method to TRUCKs. We generated IL-18-secreting TRUCKs targeting the tumor antigen GD2 using the CliniMACS Prodigy® system using a recently described “all-in-one” lentiviral vector combining constitutive anti-GD2 CAR expression and inducible IL-18. Starting with 0.84 x 108 and 0.91 x 108 T cells after enrichment of CD4+ and CD8+ we reached 68.3-fold and 71.4-fold T cell expansion rates, respectively, in two independent runs. Transduction efficiencies of 77.7% and 55.1% was obtained, and yields of 4.5 x 109 and 3.6 x 109 engineered T cells from the two donors, respectively, within 12 days. Preclinical characterization demonstrated antigen-specific GD2-CAR mediated activation after co-cultivation with GD2-expressing target cells. The functional capacities of the clinical-scale manufactured TRUCKs were similar to TRUCKs generated in laboratory-scale and were not impeded by cryopreservation. IL-18 TRUCKs were activated in an antigen-specific manner by co-cultivation with GD2-expressing target cells indicated by an increased expression of activation markers (e.g. CD25, CD69) on both CD4+ and CD8+ T cells and an enhanced release of pro-inflammatory cytokines and cytolytic mediators (e.g. IL-2, granzyme B, IFN-γ, perforin, TNF-α). Manufactured TRUCKs showed a specific cytotoxicity towards GD2-expressing target cells indicated by lactate dehydrogenase (LDH) release, a decrease of target cell numbers, microscopic detection of cytotoxic clusters and detachment of target cells in real-time impedance measurements (xCELLigence). Following antigen-specific CAR activation of TRUCKs, CAR-triggered release IL-18 was induced, and the cytokine was biologically active, as demonstrated in migration assays revealing specific attraction of monocytes and NK cells by supernatants of TRUCKs co-cultured with GD2-expressing target cells. In conclusion, GMP-compliant manufacturing of TRUCKs is feasible and delivers high quality T cell products

Hybrids of Sterically Hindered Phenols and Diaryl Ureas: Synthesis, Switch from Antioxidant Activity to ROS Generation and Induction of Apoptosis

The utility of sterically hindered phenols (SHPs) in drug design is based on their chameleonic ability to switch from an antioxidant that can protect healthy tissues to highly cytotoxic species that can target tumor cells. This work explores the biological activity of a family of 45 new hybrid molecules that combine SHPs equipped with an activating phosphonate moiety at the benzylic position with additional urea/thiourea fragments. The target compounds were synthesized by reaction of iso(thio)cyanates with C-arylphosphorylated phenols containing pendant 2,6-diaminopyridine and 1,3-diaminobenzene moieties. The SHP/urea hybrids display cytotoxic activity against a number of tumor lines. Mechanistic studies confirm the paradoxical nature of these substances which combine pronounced antioxidant properties in radical trapping assays with increased reactive oxygen species generation in tumor cells. Moreover, the most cytotoxic compounds inhibited the process of glycolysis in SH-SY5Y cells and caused pronounced dissipation of the mitochondrial membrane of isolated rat liver mitochondria. Molecular docking of the most active compounds identified the activator allosteric center of pyruvate kinase M2 as one of the possible targets. For the most promising compounds, 11b and 17b, this combination of properties results in the ability to induce apoptosis in HuTu 80 cells along the intrinsic mitochondrial pathway. Cyclic voltammetry studies reveal complex redox behavior which can be simplified by addition of a large excess of acid that can protect some of the oxidizable groups by protonations. Interestingly, the re-reduction behavior of the oxidized species shows considerable variations, indicating different degrees of reversibility. Such reversibility (or quasi-reversibility) suggests that the shift of the phenol-quinone equilibrium toward the original phenol at the lower pH may be associated with lower cytotoxicity