Specific reactions of polyfunctional proteins of the family of macroglobulins and lactoferrin with receptors and ligands in the protection of the body from pathogens

The reactions of polyfunctional proteins alpha2-macroglobulin (MG) and lactoferrin (LF) lipoprotein-receptor protein (LRP) and different ligands (antibodies and hydrolases) for ascertaining the mechanisms of their interaction and the probable role of MG and LF in the neutralization of bacterial pathogens were under study. The binding of MG and LF with ligands, irrespective of their nature, was shown to lead to the neutralization of the complex thus formed. This mechanism of neutralization in reaction of LF with ligands was supposedly due to the antibacterial properties of this protein: multiple reactions of LF with receptor sites on the surface of pathogens neutralized the charge of the latter and facilitated phagocytosis. The interaction of LRP of immunocompetent cells with MG, in the presence of additional binding sites on its surface, made it possible for MG to effectively bind and present even heretofore unknown pathogens in the presence of hydrolases on their surface.     

Long non‐coding RNAs in melanoma

Melanoma is the most lethal cutaneous cancer with a highly aggressive and metastatic phenotype. While recent genetic and epigenetic studies have shed new insights into the mechanism of melanoma development, the involvement of regulatory non‐coding RNAs remain unclear. Long non‐coding RNAs (lncRNAs) are a group of endogenous non‐protein‐coding RNAs with the capacity to regulate gene expression at multiple levels. Recent evidences have shown that lncRNAs can regulate many cellular processes, such as cell proliferation, differentiation, migration and invasion. In the melanoma, deregulation of a number of lncRNAs, such as HOTAIR, MALAT1, BANCR, ANRIL, SPRY‐IT1 and SAMMSON, have been reported. Our review summarizes the functional role of lncRNAs in melanoma and their potential clinical application for diagnosis, prognostication and treatment.     

Protective effect of bixin on carbon tetrachloride-induced hepatotoxicity in rats

Background

The liver is an important organ for its ability to transform xenobiotics, making the liver tissue a prime target for toxic substances. The carotenoid bixin present in annatto is an antioxidant that can protect cells and tissues against the deleterious effects of free radicals. In this study, we evaluated the protective effect of bixin on liver damage induced by carbon tetrachloride (CCl₄) in rats.

Results

The animals were divided into four groups with six rats in each group. CCl₄ (0.125 mL kg^-1 body wt.) was injected intraperitoneally, and bixin (5.0 mg kg^-1 body wt.) was given by gavage 7 days before the CCl₄ injection. Bixin prevented the liver damage caused by CCl₄, as noted by the significant decrease in serum aminotransferases release. Bixin protected the liver against the oxidizing effects of CCl₄ by preventing a decrease in glutathione reductase activity and the levels of reduced glutathione and NADPH. The peroxidation of membrane lipids and histopathological damage of the liver was significantly prevented by bixin treatment.

Conclusion

Therefore, we can conclude that the protective effect of bixin against hepatotoxicity induced by CCl₄ is related to the antioxidant activity of the compound.     

Level of lactoferrin in serum and cerebrospinal fluid of patients with meningitis

Study showed 9-fold increase of concentration of lactoferrin (LF) in serum of patients with bacterial meningitis (BM) compared with normal concentration and 5-fold increase of LF concentration in patients with aseptic meningitis (AM). Level of LF in cerebrospinal fluid (CSF) of patients with BM and AM was 200-fold and 22-fold higher than in control group respectively. In 71% of patients with AM concentration of protein in CSF did not exceed minimal level observed in patients with BM. Level of LF in serum and CSF during treatment statistically significantly decreased. Concentration of LF (the latter is marker of neutrophilic granulocytes activation) can be used as a characteristic of acuteness and intensity of inflammatory process in central nervous system, whereas detection of LF in CSF--as additional criterion in differential diagnostics between bacterial and viral meningitis. Furthermore, repeated measurement of LF level can be useful for monitoring of disease course and assessment of effect of treatment.     

A new species of Mesocoelium (Digenea: Mesocoeliidae) found in Rhinella marina (Amphibia: Bufonidae) from Brazilian Amazonia

Mesocoelium lanfrediaesp. nov. (Digenea: Mesocoeliidae) inhabits the small intestine of Rhinella marina (Amphibia: Bufonidae) and is described here, with illustrations provided by light, scanning electron microscopy and molecular approachs. M. lanfrediae sp. nov. presents the typical characteristics of the genus, but is morphometrically and morphologically different from the species described previously. The main diagnostic characteristics of M. lanfrediae sp. nov. are (i) seven pairs of regularly-distributed spherical papillae on the oral sucker, (ii) ventral sucker outlined by four pairs of papillae distributed in a uniform pattern and interspersed with numerous spines, which are larger at the posterior margin and (iii) small, rounded tegumentary papillae around the opening of the oral sucker, which are morphologically different from those of the oral sucker itself, some of which are randomly disposed in the ventrolateral tegumentary region of the anterior third of the body. Addionally, based on SSU rDNA, a phylogenetic analysis including Brachycoeliidae and Mesocoeliidae taxa available on GenBank established the close relationship between M. lanfrediae sp. nov. and Mesocoelium sp.     

Synthesis,modification, and cytotoxic evaluation of 2,3-secotriterpenic β-ketoesters

A set of β-ketoesters was synthesized from 2,3-seco-18αH-oleanane and 2,3-secolupane bromomethyl ketones. Additionally, hydroxy derivatives with the A-seco- or five-membered A ring were obtained as a result of the reduction or of alkaline hydrolysis of acetic acid β-ketoesters 4, 9. Cytotoxic screening revealed the compound 4 with marked activity (IC₅₀ 3.07–3.61?µM) against the HCT 116, MS, RD TE32 cancer cells. The studies of the cytotoxic mechanism enabled elucidating the fact that treatment of the HCT 116 cells with compound 4 for 18?h leads to induction of apoptosis in a dose-dependent manner. This observation was confirmed by registration of chromatin condensation, by the fluorescence increased during Annexin V-FITC staining, and by appearance of a sub-G0 peak in the cell cycle analysis with DAPI. Compound 4 also inhibited migration of cancer cells in the wound healing assay.     

Phosphorylation and biosynthesis of high molecular weight proteins of tumor nuclear matrix

INTRODUCTIONAsearlyasin1948wehavefr8CtionatedisolatednucleifromnormalandtumorcellsbyextractionwithiMNaCIanddilutealkali[1].Thenuclearresiduewasthenstudiedmorethoroughly[2,3].Lateron,sillillarproteinousnuclearresidueswereisolatedbyotherworkers[46]andasstud…     

Algorithms and software for support of gene identification experiments

MOTIVATION: Gene annotation is the final goal of gene prediction algorithms. However, these algorithms frequently make mistakes and therefore the use of gene predictions for sequence annotation is hardly possible. As a result, biologists are forced to conduct time-consuming gene identification experiments by designing appropriate PCR primers to test cDNA libraries or applying RT-PCR, exon trapping/amplification, or other techniques. This process frequently amounts to 'guessing' PCR primers on top of unreliable gene predictions and frequently leads to wasting of experimental efforts. RESULTS: The present paper proposes a simple and reliable algorithm for experimental gene identification which bypasses the unreliable gene prediction step. Studies of the performance of the algorithm on a sample of human genes indicate that an experimental protocol based on the algorithm's predictions achieves an accurate gene identification with relatively few PCR primers. Predictions of PCR primers may be used for exon amplification in preliminary mutation analysis during an attempt to identify a gene responsible for a disease. We propose a simple approach to find a short region from a genomic sequence that with high probability overlaps with some exon of the gene. The algorithm is enhanced to find one or more segments that are probably contained in the translated region of the gene and can be used as PCR primers to select appropriate clones in cDNA libraries by selective amplification. The algorithm is further extended to locate a set of PCR primers that uniformly cover all translated regions and can be used for RT-PCR and further sequencing of (unknown) mRNA.      

The possible role of alpha 2-macroglobulin in regulating the immune components of the brain in tick-borne encephalitis

In tick-borne encephalitis certain immunopathological reactions develop in the tissues of the central nervous system; alpha 2-macroglobulin may serve as the marker of the activity of these reactions. The dynamic study of liquor taken from 16 patients with the meningeal and focal forms of tick-borne encephalitis (TBE), 8 patients with severe craniocerebral traumas accompanied by meningitis and 10 patients with osteochondrosis was made. As revealed in this study, in TBE patients the level of alpha 2-macroglobulin increases 3.5-fold and remains stable during the acute period of the disease.     

Alpha-2 macroglobulin ligands and mechanisms of their biotransport

Alpha-2-macroglobulin (α2-MG) is a high-molecular weight glycoprotein with a broad spectrum of regulatory functions. As was shown earlier, covalent binding of α2-MG to proteases results in its conformational transformation, which allows α2-MG to transport additionally certain types of cytokines, attached via non-covalent interactions. Our results have shown that the spectrum of proteins exhibiting additional binding to the transformed α2-MG is rather broad and includes three classes of immunoglobulins, albumin, both types of lipoproteins, plasmin, some cytokines, and even pregnancy-associated alpha-2-glycoprotein (a structural homologue of α2-MG). The main ligands are albumin, IgG, plasmin, and to a lesser extent, lipoproteins. Interaction of native α2-MG with both acidic and weakly alkaline proteases results in neutralization net charge of the formed complex at pH, characteristic for internal media of the body. Addition of LRP (the low density lipoprotein related protein) increased the amount of electrically neutral complexes at pH 7.4. We believe that the transformed α2-MG (possibly in the complex with other effector proteins) employs similar mechanism for quick adsorption on the cell surface; after binding to LRP and repeated neutralization of the net charge at physiological pH, it “falls” through into the cell membrane and realize its regulatory functions.