Inhibitors of Sortases of Gram-Positive Bacteria and their Role in the Treatment of Infectious Diseases (Review)

Pharmaceutical Chemistry Journal - The functions of sortase bacterial enzymes and their surface-protein substrates are reviewed. Their role in the pathogenesis of infectious diseases such as...     

Isolation and characterization of A protein C activator fromAgkistrodon contortrix contortrix venom

A. L. Myasnikov Institute of Clinical Cardiology, All-Union Cardiologic Scientific Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR, I. K. Shkhvatsabaya [deceased].) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 108, No. 7, pp. 57–59, July, 1989.     

Detection of IFNγ-Secreting CD4+ and CD8+ Memory T Cells in COVID-19 Convalescents after Stimulation of Peripheral Blood Mononuclear Cells with Live SARS-CoV-2

Background: New coronavirus SARS-CoV-2, a causative agent of the COVID-19 pandemic, has been circulating among humans since November 2019. Multiple studies have assessed the qualitative and quantitative characteristics of virus-specific immunity in COVID-19 convalescents, however, some aspects of the development of memory T-cell responses after natural SARS-CoV-2 infection remain uncovered. Methods: In most of published studies T-cell immunity to the new coronavirus is assessed using peptides corresponding to SARS-CoV-1 or SARS-CoV-2 T-cell epitopes, or with peptide pools covering various parts of the viral proteins. Here, we determined the level of CD4⁺ and CD8⁺ memory T-cell responses in COVID-19 convalescents by stimulating PBMCs collected 1 to 6 months after recovery with sucrose gradient-purified live SARS-CoV-2. IFNγ production by the central and effector memory helper and cytotoxic T cells was assessed by intracellular cytokine staining assay and flow cytometry. Results: Stimulation of PBMCs with live SARS-CoV-2 revealed IFNγ-producing T-helper effector memory cells with CD4⁺CD45RA⁻CCR7⁻ phenotype, which persisted in circulation for up to 6 month after COVID-19. In contrast, SARS-CoV-2-specific IFNγ-secreting cytotoxic effector memory T cells were found at significant levels only shortly after the disease, but rapidly decreased over time. Conclusion: The stimulation of immune cells with live SARS-CoV-2 revealed a rapid decline in the pool of effector memory CD8⁺, but not CD4⁺, T cells after recovery from COVID-19. These data provide additional information on the development and persistence of cellular immune responses after natural infection, and can inform further development of T cell-based SARS-CoV-2 vaccines.     

Effects of Nanostructurized Silicon on Proliferation of Stem and Cancer Cell

In vitro experiments showed that stem and cancer cells retained their viability on the surface of porous silicon with 10-100 nm nanostructures, but their proliferation was inhibited. Silicon nanoparticles of 100 nm in size obtained by mechanical grinding of porous silicon films or crystal silicon plates in a concentration below 1 mg/ml in solution did not modify viability and proliferation of mouse fibroblast and human laryngeal cancer cells. Additional ultrasonic exposure of cancer cells in the presence of 1 mg/ml silicon nanoparticles added to nutrient medium led to complete destruction of cells or to the appearance of membrane defects blocking their proliferation and initiating their apoptotic death.     

Synthetic hydrosilicate nanotubes induce low pro‐inflammatory and cytotoxic responses compared to natural chrysotile in lung cell cultures

Asbestos (Mg‐hydrosilicate; chrysotile) is known to cause pleural diseases, pulmonary fibrosis and lung cancers, via mechanisms strongly depending on diameter‐length ratio and possibly metal content. A critical question is whether synthetic hydrosilicate nanotubes (NTs) of short length possess little toxic potential compared to chrysotile. Five Mg‐ and two NiNTs of different lengths were assessed for cytotoxicity and pro‐inflammatory responses in THP‐1 macrophages and human bronchial epithelial lung cells (HBEC3‐KT), in comparison with chrysotile. NT lengths/diameters were characterized by TEM, surface areas by BET‐ and BJH analysis, and chemical composition by XRD. The different Mg‐ and NiNTs induced little cytotoxicity in both cell models, in contrast to chrysotile that induced marked cytotoxicity. The two longest synthetic MgNTs, with median lengths of 3 and 5 µm, induced increased levels of pro‐inflammatory cytokines in THP‐1 macrophages, but much less than chrysotile (median length 15 µm) and silica nanoparticles (Si10). The shortest NTs did not induce any increase in cytokines. In HBEC3‐KT cells, all synthetic NTs induced no or only small changes in cytokine responses, in contrast to chrysotile and Si10. The synthetic NTs induced lower TGF‐β responses than chrysotile in both cell models. In conclusion, the pro‐inflammatory responses were associated with the length of synthetic hydrosilicate NTs in THP‐1 macrophages, but not in HBEC3‐KT cells. Notably, the shortest NTs showed no or little pro‐inflammatory activity or cytotoxicity in both cell models. Such a safety by design approach is important for development of new materials being candidates for various new products.