Protection Activity of 1,4-Naphthoquinones in Rotenone-Induced Models of Neurotoxicity.

The MTS cell viability test was used to screen a mini library of natural and synthetic 1,4-naphthoquinone derivatives (1,4-NQs) from marine sources. This screening identified two highly effective compounds, U-443 and U-573, which showed potential in protecting Neuro-2a neuroblastoma cells from the toxic effects of rotenone in an in vitro model of neurotoxicity. The selected 1,4-NQs demonstrated the capability to reduce oxidative stress by decreasing the levels of reactive oxygen species (ROS) and nitric oxide (NO) in Neuro-2a neuroblastoma cells and RAW 264.7 macrophage cells and displayed significant antioxidant properties in mouse brain homogenate. Normal mitochondrial function was restored and the mitochondrial membrane potential was also regained by 1,4-NQs after exposure to neurotoxins. Furthermore, at low concentrations, these compounds were found to significantly reduce levels of proinflammatory cytokines TNF and IL-1ß and notably inhibit the activity of cyclooxygenase-2 (COX-2) in RAW 264.7 macrophages. The results of docking studies showed that the 1,4-NQs were bound to the active site of COX-2, analogically to a known inhibitor of this enzyme, SC-558. Both substances significantly improved the behavioral changes in female CD1 mice with rotenone-induced early stage of Parkinson's disease (PD) in vivo. It is proposed that the 1,4-NQs, U-443 and U-573, can protect neurons and microglia through their potent anti-ROS and anti-inflammatory activities.

Holothurian triterpene glycoside cucumarioside A2-2 induces macrophages activation and polarization in cancer immunotherapy.

BACKGROUND: Despite intensive developments of adoptive T cell and NK cell therapies, the efficacy against solid tumors remains elusive. Our study demonstrates that macrophage-based cell therapy could be a potent therapeutic option against solid tumors. METHODS: To this end, we determine the effect of a natural triterpene glycoside, cucumarioside A2-2 (CA2-2), on the polarization of mouse macrophages into the M1 phenotype, and explore the antitumor activity of the polarized macrophage. The polarization of CA2-2-pretreated macrophages was analyzed by flow cytometry and confocal imaging. The anti-cancer activity of CA2-2 macrophages was evaluated against 4T1 breast cancer cells and EAC cells in vitro and syngeneic mouse model in vivo. RESULTS: Incubation of murine macrophages with CA2-2 led to polarization into the M1 phenotype, and the CA2-2-pretreated macrophages could selectively target and kill various types of cancer in vitro. Notably, loading near-infrared (NIR) fluorochrome-labeled nanoparticles, MnMEIO-mPEG-CyTE777, into macrophages substantiated that M1 macrophages can target and penetrate tumor tissues in vivo efficiently. CONCLUSION: In this study, CA2-2-polarized M1 macrophages significantly attenuated tumor growth and prolonged mice survival in the syngeneic mouse models. Therefore, ex vivo CA2-2 activation of mouse macrophages can serve as a useful model for subsequent antitumor cellular immunotherapy developments.

Study of the Effect of Selective Media with High Doses of Zinc on Regeneration Ability and Rutin Accumulation in Common Buckwheat In Vitro.

Biotechnological methods are widely used in modern common buckwheat (Fagopyrum esculentum Moench) studies, constitute an effective tool to create the best agronomic traits of the crop, and can also be used to breed forms, resistant to heavy metal ion toxicity, which is important in the environment of constantly growing anthropogenic pressure on ecosystems. The studied high concentrations of zinc salts (808-1313 mg L-1) in the nutrient medium in vitro had an inhibitory effect on buckwheat, which was manifested by a decrease in values of its morphological indicators. Ion stress had an adverse effect on 7-9% of plants from their total number, indicating high plasticity and resistance of F. esculentum to highly toxic doses of zinc. The stress state of F. esculentum significantly increases the production of flavonoid compounds, including rutin, in plant cells, which is used in biotechnology to assess and obtain buckwheat forms of high flavonoid induction capacity. The processes of rutin biosynthesis were most intense in test-tube plants of the Izumrud × Inzerskaya hybrid obtained after exposure to high doses of zinc 1010-1212 mg L-1. F. esculentum genotypes obtained using selective backgrounds with high zinc concentrations are promising biosystems for synthesis of rutin, valuable for pharmacology and medicine.

Influence of Merosesquiterpenoids from Marine Sponges on Seedling Root Growth of Agricultural Plants.

The impact of the merosesquiterpenoids avarol (1), avarone (2), 18-methylaminoavarone (3), melemeleone A (4), isospongiaquinone (5), ilimaquinone (6), and smenoquinone (7), isolated from marine sponges of the Dictyoceratida order, was studied on the root growth of seedlings of buckwheat (Fagopyrumesculentum Moench), wheat (Triticumaestivum L.), soy (Glycine max (L.) Merr.), and barley (Hordeumvulgare L.). Compounds 2and 6 were effective for the root growth of wheat seedlings, compound 3 stimulated the root growth of seedlings of buckwheat and soy, compound 4 affected the roots of barley seedlings, and compound 5 stimulated the root growth of seedlings of buckwheat and barley. Compounds 1 and 7 showed no activity on the root growth of the seedlings of any of the studied plants. The stimulatory effect depends on the chemical structure of the compounds and the type of crop plant.

Influence of the Metabolites of the Marine Algicolous Fungus Penicillium sp. on Seedling Root Growth of Agricultural Plants.

N-Methylpretrichodermamide B (I), pretrichodermamide C (H), quinolactacide (III) and 8-methoxy-3,5-dimethyl-3,4-dihydro-IH-isochromen-6-ol (IV), isolated from the marine fungus Penicillium sp., were examined for their ability to stimulate growth of seedling roots of buckwheat (Fagopyrum esculentum Moench), wheat (Triticum aestivum L.), soy {Glycine max (L.) Merr.}, and barley (Hordeum vulgare), It was shown that the stimulatory effects depend on the chemical structure of the compounds and on the plant species. Compounds I and III improved the rate of growth of seedling roots of buckwheat (1) and wheat (2), compound II stimulated growth of buckwheat roots (1), and compound IV improved growth of seedling roots of wheat (2) and soy (3). These compounds can be recommended for field study as plant growth stimulators.

Oxirapentyns A, B and E from the marine-derived strain of Isaria felina KMM 4639 as stimulators of initial stages of development of agricultural plants.

Oxirapentyn A (1), oxirapentyn B (2), and oxirapentyn E (3) were examined for their ability to stimulate growth of seedling roots of barley (Hordeum vulgare L.), buckwheat (Fagopyrum esculentum Moench), corn (Zea mays L.), soy {Glycine max (L.) Merr.}, and wheat (Triticum aestivum L.). It was shown that the stimulatory effects depend on the chemical structure of the oxirapentyns and on the plant species. Compounds 1, and 2 are efficient for growth of seedling roots of barley, and wheat, whereas compound 3, at different concentrations, stimulates growth of seedling roots of maize, soy, and wheat. These compounds can be recommended for field study as plant growth stimulators.

Alkaloids from marine sponges as stimulators of initial stages of development of agricultural plants.

Damirone A (1), damirone B (2), makaluvamine G (3), debromohymenialdisine (4), and dibromoagelaspongin (5) were examined for their ability to stimulate growth of seedling roots of barley (Hordeum vulgare L.), buckwheat (Fagopyrum esculentum Moench), corn (Zea mays L.), soy (Glycine max (L.) Merr.}, and wheat (Triticum aestivum L.). It was shown that the stimulatory effects depend on the chemical structure of the alkaloids and on the plant species. Compounds 1, 3, and 4 are efficient for growth of seedling roots of barley, compounds 2-5, at different concentrations, stimulate growth of buckwheat roots, and compound 5 stimulates growth of wheat roots. These compounds can be recommended for field study as plant growth stimulators.

Fabrication, characterization, and theoretical analysis of controlled disorder in the core of optical fibers.

We present results of experimental and theoretical studies of polarization-resolved light transmission through optical fiber with disorder generated in its germanium-doped core via UV radiation transmitted through a diffuser. In samples longer than a certain characteristic length, the power transmitted with preserved polarization is observed to be distributed over all forward-propagating modes, as evidenced by the Rayleigh negative exponential distribution of the near-field intensity at the output surface of the fiber. Furthermore, the transmitted power becomes also equally distributed over both polarizations. To describe the optical properties of the fibers with the experimentally induced disorder, a theoretical model based on coupled-mode theory is developed. The obtained analytical expression for the correlation function describing spatial properties of the disorder shows that it is highly anisotropic. Our calculations demonstrate that this experimentally controllable anisotropy can lead to suppression of the radiative leakage of the propagating modes, so that intermode coupling becomes the dominant scattering process. The obtained theoretical expressions for the polarization-resolved transmission fit very well with the experimental data, and the information extracted from the fit shows that radiative leakage is indeed small. The reported technique provides an easy way to fabricate different configurations of controlled disorder in optical fibers suitable for such applications as random fiber lasers.

Polar steroidal compounds from the far eastern starfish Henricia leviuscula.

Five new polar steroids, polyhydroxysterols 2-5 and the glycoside leviusculoside J (7), were isolated, along with the previously known compounds 1, 6, 8, and 9, from the alcoholic extract of the Far Eastern starfish Henricia leviuscula. The structures of novel compounds were elucidated by interpretation of spectral data (mainly 2D-NMR), and the stereochemistry of chiral centers in the side chain of sterols 2 and 3 was determined by using J-based configuration analysis and the modified Mosher's method. Steroids 1, 3, 6, 7, and 9 showed moderate hemolytic activity in the mouse erythrocytes assay.

Biological activities of marine sesquiterpenoid quinones: structure-activity relationships in cytotoxic and hemolytic assays.

Sesquiterpenoid quinones from marine sponges and their semisynthetic derivatives were compared for cytotoxicity on developing eggs of sea urchin Strongylocentrotus nudus and Ehrlich carcinoma cells, and for hemolytic activities on mice red blood cells. Structure-activity studies showed that activities of these compounds with a hydroxyl group at C-20 ((2), (7)) were higher than their methoxyl ((1), (8)) and amino ((4), (5)) derivatives at this position. Sesquiterpenoid quinones containing a dihydropyran ring ((10)-(12)) had lower activity than noncyclic compounds. The structure of the terpenoid moieties of the compounds had no significant influence on biological activity. There was a direct correlation between cytotoxic and hemolytic activities. This report discusses the mechanism of action employed by these compounds against cell membranes.

Biological activities of steroid glycosides from starfish.

Glycosides of polyhydroxysteroids from starfish were compared with regard to hemolytic activities on mouse red blood cells and cytotoxicity on developing eggs of sea urchin Strongylocentrotus intermedius. Mediasteroside M(1) from Mediaster murrayi with a 2-O-methyl group at a xylose residue exerted lower activity than mediasteroside M(2) without this group. Ceramasteroside C(2) from Ceramaster patagonicus having a 2,4-di-O-Me-Xylp residue had more activity in comparison with ceramasteroside C(3) with 2-O-Me-Xylp. Activities of rathbuniosides R(1) (four OH-groups) and R(2) (five OH-groups) from Asterias rathbuni, and culcitosides C(2) (six OH-groups) and C(3) (five OH-groups) from Culcita novaeguineae were inversely proportional to the number of hydroxyl groups of the aglycon. There was a correlation between cytotoxic and hemolytic activities. The results indicated that salt concentration, temperature and pH values are important for the hemolytic activity of steroid glycosides.