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The growth of microbial multidrug resistance is a problem in modern clinical medicine. Chemical modification of active pharmaceutical ingredients is an attractive strategy to improve their biopharmaceutical properties by increasing bioavailability and reducing drug toxicity. Conjugation of antimicrobial drugs with natural polysaccharides provides high efficiency of these systems due to targeted delivery, controlled drug release and reduced toxicity. This paper reports a two-step synthesis of colistin conjugates (CT) with succinyl chitosan (SucCS); first, we modified chitosan with succinyl anhydride to introduce a carboxyl function into the polymer molecule, which was then used for chemical grafting with amino groups of the peptide antibiotic CT using carbodiimide chemistry. The resulting polymeric delivery systems had a degree of substitution (DS) by CT of 3–8%, with conjugation efficiencies ranging from 54 to 100% and CT contents ranging from 130–318 μg/mg. The size of the obtained particles was 100–200 nm, and the ζ-potential varied from −22 to −28 mV. In vitro release studies at pH 7.4 demonstrated ultra-slow hydrolysis of amide bonds, with a CT release of 0.1–0.5% after 12 h; at pH 5.2, the hydrolysis rate slightly increased; however, it remained extremely low (1.5% of CT was released after 12 h). The antimicrobial activity of the conjugates depended on the DS. At DS 8%, the minimum inhibitory concentration (MIC) of the conjugate was equal to the MIC of native CT (1 µg/mL); at DS of 3 and 5%, the MIC increased 8-fold. In addition, the developed systems reduced CT nephrotoxicity by 20–60%; they also demonstrated the ability to reduce bacterial lipopolysaccharide-induced inflammation in vitro. Thus, these promising CT-SucCS conjugates are prospective for developing safe and effective nanoantibiotics. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We propose a new method of cancer diagnostics based on identification of characteristic cancer spectral lines in the frequency range of 0.1-2THz. Using terahertz spectral database of normal and pathological human tissues we could monitor the slightest changes caused by the appearance of cancer at the early stages. [ABSTRACT FROM AUTHOR]

In order to ensure safety in the use of terahertz radiation for medical problems, impact assessment of broadband terahertz radiation in the frequency range of 0.05-1.7 THz was made to investigate functional activity of tumor cells in vitro. According to the results of flow cytometry we can speculate that pulsed terahertz radiation with a power density of up to near 10mW/cm² and duration of 1 minute does not change functional activity of tumor cells. [ABSTRACT FROM AUTHOR]

According to the literary data, terahertz radiation has some effects on different blood cells. Our study focuses on the determining the level of some cell surface antigens of lymphocytes when exposed to broadband terahertz range of 0.05-1.70 THz. These data indicate that terahertz radiation with power density of 9.55, 0.63 and 0.03 mW/cm² for 1 minute does not alter the functional activity of lymphocytes. [ABSTRACT FROM AUTHOR]

Adiponectin is an adipose tissue hormone affecting energy and lipoprotein metabolism and modulating inflammatory responses. However, the role of this adipokine in atherogenesis remains poorly understood. The aim of this study was to investigate the effect of adiponectin on the production of apolipoproteins (apo) A-l and E by human macrophages (MP). The study was conducted on macrophage-like cells of the THP-1 cell line of two differentiation terms, 3 and 5 days (3d and 5d). Adiponectin (10 μg/mL) stimulated the expression of apoA-1 gene at the mRNA level in 5d MP, but not in 3d MP. The level of apoE mRNA in MP under the action of adiponectin was not affected. Adiponectin suppressed macrophage TNF gene expression, while it induced the expression of IL-10 gene in 5d MP. The secreted levels of apoA-1 and apoE proteins under the action of adiponectin in macrophages of both periods of differentiation remained unchanged, while the level of the surface apoA-1 protein in 5d MP was decreasing. Incubation of 5d MP with the PPARα nuclear receptor antagonist MK-886 or with the nuclear receptor LXR agonist TO-901317 resulted in cancellation of the stimulating effect of adiponectin on apoA-1 gene expression. These data indicate that adiponectin, in addition to its anti-inflammatory action, has a modulating effect on production of apoA-1 by macrophages. The latter is probably one of the mechanisms of the influence of this adipokine on atherogenesis.