Marine Organisms as Alkaloid Biosynthesizers of Potential Anti-Alzheimer Agents

The incidence of neurodegenerative diseases, such as Alzheimer’s disease (AD), increases continuously demanding the urgent development of anti-Alzheimer’s agents. Marine organisms (MO) have to create their own defenses due to the adverse environment where they live and so synthesize several classes of compounds, such as akaloids, to defend themselves. Therefore, the identification of marine natural products with neuroprotective effects is a necessity. Being that AD is not only a genetic but also an environmental complex disease, a treatment for AD remains to discover. As the major clinical indications (CI) of AD are extracellular plaques formed by β-amyloid (Aβ) protein, intracellular neurofibrillary tangles (NFTs) formed by hyper phosphorylated τ-protein, uncommon inflammatory response and neuron apoptosis and death caused by oxidative stress, alkaloids that may decrease CI, might be used against AD. Most of the alkalolids with those properties are derivatives of the amino acid tryptophan mainly with a planar indole scaffold. Certainly, alkaloids targeting more than one CI, multitarget-directed ligands (MTDL), have the potential to become a lead in AD treatment. Alkaloids to have a maximum of activity against CI, should be planar and contain halogens and amine quaternization.

Peculiarities of synthesis and bactericidal properties of nanosilver in colloidal solutions, SiO2 films and in the textile structure: a review

The aim of this work is a comparative analysis of the biocidal efficiency of Ag nanoparticles (NPs) in the colloidal state, in the structure of films and dispersions of SiO2 and in the composition of textile fabrics, dependent on the method of synthesis, based on literature data and on own researches. Chemical reduction of silver (with borohydrides, hydrogen, hydrazine, etc.) allows one to adjust and control the size and shape of NPs. The shape of the NPs is mostly spherical, what is confirmed by the presence of a band of surface plasmon resonance in absorption spectra and by electron microscopy measurements. To prevent aggregation of NPs obtained by the method of chemical reduction in solution, the optimal ratio of two stabilizers based on surfactants and polymer at their minimum concentration was found, namely NaBH4 as a reductant and polyvinylpyrrolidone + sodium dodecyl sulfate as binary stabilizer of Ag NPs, with bactericidal activity of 99 % and stability for more than 3 years. Chemical reduction of silver ions was carried out also by the amino acid tryptophan (Trp) which has a dual function – a biocompatible reducing agent and stabilizer of silver NPs while maintaining their shape, size and stability for long-term use. Effective methods of photochemical synthesis of Ag NPs have been developed in different ways: by UV irradiation of Ag+ ions in solution in the presence of solid-state photosensitizer SiO2 with adsorbed benzophenone (SiO2/BPh); by UV irradiation of Ag+ ions in solution in the presence of the amino acid tryptophan (Trp); on silica surface when Ag/SiO2 sol-gel films production via irradiation of adsorbed Ag+ ions on SiO2 film (Ag+/SiO2) in the BPh solution. It is shown that when Ag NPs are adsorbed on the surface of highly dispersed SiO2, the logarithm of the reduction of microorganisms reduces and the time of their deactivation increases. A cheap and convenient way to modify of cotton textiles with Ag NPs by soft heat treatment of Ag+/cotton samples with high (90–95 %) efficiency of destruction of bacteria E. coli, K. pneumoniae, E. aerogenes, P. vulgaris, S. aureus, C. albicans, etc., with saving of biocidal activity after 5 cycles of washing has been developed. The dynamics of silver ions release from the surface of NPs in the structure of textile upon their contact with water for 72 hours and the number of irreversibly bound particles have been studied. The electrical resistance of the tissue is proportional to the quantity of NPs. That is NPs in the structure are in different degrees of binding, a certain part of them is retained (adsorbed) irreversibly, saving bactericidal properties after repeated contacts with water. On the basis of literature analysis it is shown that ecologically safe “green synthesis” is a promising way to silver NPs produce with pronounced bactericidal efficiency, which is becoming more common due to the large resource of cheap plant raw materials.

A new replication medium enables a rapid identification of φx-174 virus by synchronous fluorescence of Tryptophan.

Development of rapid methods for identification of bacteriophages based on their intrinsic fluorescence is challenging. Pure bacteriophages may be detected based on the strong fluorescence of the amino acid Tryptophan that exist in their proteins. Nevertheless, Tryptophan is a molecule that also exist in high quantities in the bacterial hosts and their cultivation media. In this work, we show that simple separation of the bacteriophage φx-174 from its E.coli host (grown on standard cultivation medium) by filtration is not sufficient for its identification based on the intrinsic fluorescence of its Tryptophan content. This is mostly because of the tryptophan residues that derive from the cultivation medium. We fabricate a new cultivation medium that does not have any significant fluorescence overlap with Tryptophan. By utilization of this new cultivation medium, we can identify φx174 based on the spectral fingerprint of its intrinsic Tryptophan content by synchronous fluorescence measurements.

Galectin-anchored indoleamine 2,3-dioxygenase suppresses local inflammation

Chronic inflammation underlies the onset, progression and associated pain of numerous diseases. Current anti-inflammatory treatments administered systemically are associated with moderate-to-severe side effects, while locally administered drugs have short-lived efficacy, and neither approach successfully modifies the underlying causality of disease. We report a new way to locally modulate inflammation by fusing the enzyme indoleamine 2,3-dioxygenase 1 (IDO) to galectin-3 (Gal3). A general regulator of inflammation, IDO is immunosuppressive, catabolizing the essential amino acid tryptophan into kynurenine. Recently we demonstrated that extracellular exogenous IDO regulates innate immune cell function, and envisioned delivering IDO into specific tissues would provide control of inflammation. However, proteins problematically diffuse away from local injection sites. Addressing this, we recently established that fusion to Gal3 anchors enzymes to tissues via binding to extracellular glycans. Fusion protein IDO-Gal3 was retained in injected tissues and joints for up to a week or more, where it suppressed local inflammation in rodent models of endotoxin-induced inflammation, psoriasis, periodontal disease and osteoarthritis. Amelioration of local inflammation, disease progression and inflammatory pain were concomitant with homeostatic preservation of tissues without global immune suppression. Thus, IDO-Gal3 presents a new concept of anchoring immunomodulatory enzymes for robust control of focal inflammation in multiple disease settings.

Fusarochromene, a novel tryptophan-derived metabolite from Fusarium sacchari

Fusarochromene and the fusarochromanone mycotoxins are derived via oxidative cleavage of the aromatic amino acid tryptophan.

Micronutrient and Antinutritional Content of Weaning Food Produced from Blends of Millet, Soya Beans and Moringa Oleifera Leaf Flour

Any Weaning food offered to infants should be rich in micronutrients and high in protein quality. The study assessed the Mineral, Vitamin A and C, Amino acids and Antinutritional profile of weaning food blends from millet flour (MLF), soya beans flour (SBF) and moringa oleifera leaf flour (MLF) in the ratio FMF:SBF:MLF- sample C (60:35:5), sample D (60:30:10), sample E (60:25:5), sample F (60:20:20) sample A (100 % FMF) was used as control, sample B (FMF(60):SBF(40). All analyses were done using standard methods. The Mineral, Vitamin A, C and Amino acid Tryptophan contents of the weaning food formulations significantly (p<0.05) increased with increased MLF Percentage. The Mineral values ranged from 57.37 to 466.87 mg/100g, 11.33 to 107.30 mg/100g, 36.27 to 62.38 mg/100g, 2.45 to 4.77 mg/100g and 76.64 to 178.09 mg/100g for calcium, iron, potassium, zinc and sodium respectively. Vitamins A (ß-Carotene) and C ranged from 0-5.25 and 0.58-3.89 mg/100g respectively. Tryptophan ranged from 1.16-2.40 g/100g protein. Manganese, Lysine, methionine was significantly (p<0.05) higher in MLF unsubstituted sample B. The anti-nutrients analyzed were significantly (p<0.05) low with values ranging from (0.09 to 0.43) mg/100 g, (0.13 to 1.49) mg/100 g, (0.33 to 0.95) mg/100 g and (0.03 to 0.07) mg/100 g for phytates, tannins, oxalates and trypsin inhibitor respectively.

Kynurenic acid in brain function and dysfunction

The essential amino acid tryptophan is degraded primarily by the kynurenine pathway, a cascade of enzymatic steps leading to the generation of several neuroactive compounds. Of those, kynurenic acid (KYNA), an antagonist at N-methyl-D-aspartate (NMDA) and alpha7-nicotinic receptors, has gained much attention in schizophrenia research. The concentrations of both KYNA and its precursor, kynurenine, have been repeatedly found significantly elevated both in the postmortem cerebral cortex and in the cerebrospinal fluid of schizophrenia persons as compared to healthy control subjects. Studies in experimental animals have demonstrated that KYNA tightly controls dopaminergic, cholinergic, glutamatergic, and GABAergic neurotransmission, and elevated brain levels appear related to psychotic symptoms and cognitive impairments. The kyurenine pathway is highly inducible by immune activation, and studies have shown that the pro-inflammatory cytokines interleukin (IL)-1β‎ and IL-6 are elevated in schizophrenia and stimulate the production of KYNA. Another mechanism that may account for the abnormally high central kynurenine and KYNA levels seen in schizophrenia might be the observed reduced expression and activity of the enzyme kynurenine 3-monooxygenase (KMO), shunting the synthesis of kynurenine toward KYNA. In line with these studies and concepts, preclinical results suggest that inhibition of kynurenine aminotransferase (KAT) II, by reducing the synthesis and function of KYNA in the brain, offers a novel approach to ameliorate psychosis and to improve cognitive performance in persons with schizophrenia.