Water-soluble Form Research Articles

CHANGES IN BEHAVIOURAL REACTIONS OF RATS FOLLOWING MODELLED TRAUMATIC BRAIN INJURY AND THEIR CORRECTION WITH TRANSCRIPTION FACTORS MODULATORS

This study aimed at investigating the effect of modulators of transcription factors NF-κB, AP-1 and Nrf2 on the behavioural responses of rats in the "Dark-light chamber" and "Open field" tests following the simulation of traumatic brain injury (TBI). The study included 42 white Wistar male rats weighing 180-220 g, divided into 6 groups of 7 rats in each: the control group included the animals exposed to the above mentioned tests before TBI modelling and 3 – 7 days after it; as for the animals of other groups, for 7 days after TBI simulation they were given intraperitoneal injections of the following transcription factor modulators: ammonium pyrrolidine dithiocarbamate, an inhibitor of nuclear translocation NF-κB, was injected in a dose of 76 mg/kg; AP-1 SR 11302 inhibitor given in a dose of 1 mg/kg; Nrf2 inductors as dimethyl fumarate given in a dose of 15 mg/kg of a 10% dimethyl sulfoxide solution and epigallocatechin-3-gallate in a dose of 1 mg/kg as well as a water-soluble form of quercetin (corvitin), which acts as an NF-κB inhibitor and Nr inducer, in a dose of 100 mg / kg (10 mg / kg in terms of quercetin). Unlike the test animals, the rats of the control group were given intraperitoneal injections of 1 ml of isotonic sodium chloride solution. It has been found out that during the first week following TBI simulation, the locomotor activity and psycho-emotional state of the rats were disturbed: the indicators of motor and exploratory activity, orienting reaction became deteriorated, anxiety and fear increased as well as the frequency of self-grooming actions. The use of inhibitors of transcription factors NF-κB (ammonium pyrolidindithiocarbamate) and AP-1 (SR 11302), Nrf2 inducers (dimethyl fumarate and epigallocatechin-3-gallate) and the water-soluble form of quercetin (corvitin) for the 1st week after TBI simulation improves motor performance and exploratory activity, orienting reaction, and reduces emotional anxiety and fear as well.

Study of leaching processes of sintered black shale ore

This paper presents the results of physical and chemical investigation of black shale ore, as well as the investigation of combination of hydro- and pyrometallurgical methods in the sintering process of black shale ore with ammonium hydrosulfate to convert metals into water-soluble form. The homogeneous composite of black shale ore taken for the study consists of 67 % SiO2, 18 % C and 3 % H2O, 0.683 % V, 0.0415 Mo, 0.0148 % U3O8 and other components. Thermogravimetric analysis of sintering of carbon-silica ore with ammonium hydrosulfate in the presence of sulfuric acid was performed in the temperature range 20-1000 °C. It is established that at low-temperature sintering of ore with hydrosulfate ammonium after further leaching with sulfuric acid solution the extraction of uranium, vanadium, molybdenum and rare earth metals is 98.2 %, 91.3 %, 82.2% and 78.3 % respectively. The optimal leaching temperature is 90 °C, the ratio S: L = 1:3, and the leaching time is 2 hours.

THE COMPOSITION AND ANTIOXIDATIVE ACTIVITY OF SPRUCE ROOTS’ EXTRACT

The spruce Picea abies (L.) (Pinaceae) roots are logging residues and are not used nowadays. However, spruce roots are a source of valuable biologically active substances that have potential for medical use. The purpose is to research the composition of phenol compounds and antioxidative activity of spruce roots water extract. The raw materials for the research were the spruce roots collected on a cutting area on the day of sawing a tree. Water extract was obtained from the roots, and then polysaccharides were removed from it. Composition of the extract phenol compounds was determined using a high performance liquid chromatography on the chromatograph Agilent 1100. Compounds identification was based on retention times. Extract’s antioxidative activity was determined by the reaction with the stable radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), the EC50 value computed. Ascorbic acid and trolox (a water-soluble form of vitamin E) were used as standard substances. As a result, it was found that flavonoids, hydroxycinnamic acids, phenolcarboxylic acids are present in the spruce roots water extract. Ferulic acid has the highest amount amongst hydroxycinnamic acids in the spruce roots water extract, hyperoside – amongst flavonoids. It was found that the spruce roots water extract, without polysaccharides, has a pronounced antioxidative activity similar in strength to ascorbic acid, which allows us to talk about the prospects for further researches and the medicinal drugs manufacturing.

Effect of foliar application of liquid organic and inorganic fertilizers along with NAAon cowpea (Vigna unguiculata)

Cowpea (Vigna unguiculata) is popularly known as lobia in India, now cultivated throughout the tropics and sub-tropics and used as pulse, green vegetable, fodder, green manure and its productivity is 683 kg ha -1.Vermiwash is a liquid leachate that is collected after the passage of water through the column of worm action. It is a collection of excretory products and mucous secretion of earthworms along with micronutrients from the soil organic molecules. This bio-liquid is rich in nutrients, microorganisms, enzymes, vitamins and plant growth hormones which increase the resistant power of crops against various diseases and enhances the productivity of crops.. The nutrients present in vermiwash are in water-soluble form and meet the immediate requirements of crop plants. Further, it contains nitrogen fixing and nutrient solubilizing bacteria. Generally, foliar spray of vermiwash of vermicomposting supplies nutrients to higher plants more rapidly than soil and root application methods. Vermiwash spray persists on leaf surface and resulted in leaf thickness, increase in photosynthetic activity, internode growth, improved plant physiology and finally increased the yield (Selladuraiet al., 2009). Humic acid is a commercial product containing many elements which improve the growth and yield of cowpea. The fermented organic liquid fertilizer panchagavya contains nutrients, plant growth regulators and microorganisms which help in plant growth, yield, metabolic activities and gives resistant to pest and diseases. The commercial seaweed extract contains major and minor nutrients, amino acids, vitamins and other growth promoting substances. DAP is a complex fertilizer containing 18 % nitrogen and 46 % phosphorus. The Naphthalene acidic acid is a auxin and very effective in promoting growth and yield of pulses. It may be concluded from the results that the foliar application of 2 % DAP along with 40 ppm NAA is recommended to cowpea to enhance the yield and to obtain higher returns.

Simultaneous immobilization of Pb, Cd and As in soil by hybrid iron-, sulfate- and phosphate-based bio-nanocomposite: Effectiveness, long-term stability and bioavailablity/bioaccessibility evaluation

Here, the bio-nanocomposite (n-HFP + n-HFS)@An was developed to simultaneously immobilize Pb, Cd and As in the severely contaminated soil. The immobilization rates of diethylenetriaminepentaacetic acid (DTPA)/decarbonate-extracted bioavailable Pb, Cd and As were 59.87%, 31.28% and 62.30%, and the immobilization rates of their water-soluble forms were 63.12%, 60.02% and 89.39%, respectively. Moreover, the ten-year acid rain simulated leaching assay showed that the maximum cumulative release contents of Pb, Cd and As in the treated soil samples were decreased by 2.94, 2.46 and 40.60 times, comparing to the un-treated ones. Additionally, the results of SBRC (Solubility Bioaccessibility Research Consortium) revealed that the bioaccessible rates of the three metals in intestinal phase were lower than in gastric phase, and both of them decreased with increasing the immobilization time. The gastric bioaccessibility of Pb, Cd and As had a higher correlation with the contents of water-soluble forms, while the intestinal bioaccessibility was more strongly positively associated with the bioavailable forms.

TMOD-27. EFFICACY OF SOLUBLE PANOBINOSTAT (MTX110) IN PRECLINICAL MODELS OF ADULT GLIOBLASTOMA

Abstract INTRODUCTION Panobinostat is a histone deacetylase (HDAC) inhibitor with antineoplastic and anti-angiogenic effects in glioma. HDAC inhibitors have demonstrated therapeutic efficacy preclinically via multiple mechanisms, including the induction of cell-cycle arrest, differentiation, senescence, apoptosis, mitotic cell death, autophagy, generation of reactive oxygen species, inhibition of angiogenesis and metastasis, and improvement in tumor immunity. One of the biggest challenges in treating glioblastoma is achieving effective local drug concentrations, and trials using systemic administration of therapeutics have failed in GBM despite compelling pre clinical evidence. MTX110 (Midatech Pharma plc) is a water-soluble form of panobinostat currently in clinical development for DIPG and medulloblastoma using direct tumour delivery. We explored the therapeutic potential of MTX110 in GBM in our preclinical in vivo adult brain tumor models. METHODS Tumor-bearing mice were stratified to either the vehicle control or treatment group based on median tumor volume and were treated with Panobinostat/MTX110 at a dose of 15mg/kg IP, twice weekly for 5 consecutive weeks. The response to treatment was assessed by delay in tumor growth in days, expressed as a T (Treated) - C (Control) value. Statistical analysis was performed using SAS (a statistical analysis program) and the Wilcoxon rank order test. RESULTS MTX110 produced non-significant growth delays of 10.76 and 2.01 days (p Value ≥ 0.072 NS) in IDH wild type xenograft lines. However, in an IDH1 mutated line, MTX110 produced a significant growth delay of 23.35 days (p Value ≤ 0.018). Further work is ongoing to look at the therapeutic potential of MTX110 in combination with radiation in both IDH wild type and IDH mutated xenograft lines.

Multi-carbohydrase effects on energy utilization depend on soluble non-starch polysaccharides-to-total non-starch polysaccharides in broiler diets

Non-starch polysaccharides (NSP), especially in water-soluble form, are a common anti-nutritional factor in cereal-based poultry diets. Consequently, carbohydrases are applied to diets to combat the negative effects of NSP on bird performance and health, particularly when feeding viscous grains. This study investigated the effect of supplementing multi-carbohydrases (MC) to broiler diets containing either low (LS) or high (HS) soluble NSP (sNSP) to total NSP (tNSP) ratios on energy partitioning, nitrogen (N) balance, and performance. A 2 × 2 factorial arrangement of treatments (MC, no or yes; sNSP/tNSP, LS vs. HS) was applied, resulting in 4 dietary treatments, each replicated 8 times. These treatments were fed to Ross 308 broilers in closed-circuit indirect calorimetry chambers, with 2 birds (a male and a female) per replicate chamber (n = 64). The results showed that MC addition increased AME, net energy (NE), and AME/gross energy, regardless of sNSP/tNSP content (P < 0.01 for all). There was an MC × sNSP/tNSP interaction for feed intake (FI, P < 0.05), denoting that in the absence of MC, the HS-fed birds had lower FI than LS-fed birds, but this difference was eliminated when MC was present. There were MC × sNSP/tNSP interactions observed for AME intake (AMEi) per metabolic BW (BW0.70, P < 0.05), AMEi/N retention (Nr, P < 0.01), NE intake (NEi)/Nr (P < 0.05), retained energy (RE) as fat per total RE (REf/RE, P < 0.01), and N efficiency (Nr/N intake, P < 0.05). These interactions showed that MC application increased AMEi/BW0.70, AMEi/Nr, NEi/Nr, and REf/RE only in the HS-fed birds, and N efficiency only in the LS-fed broilers. This study demonstrated that MC application markedly increased feed energy utilization in all diets, and increased N efficiency in birds fed an LS diet.

Дослідження токсичності й антиоксидантної активності ліпосомальних антиоксидантів на моделі Paramecium caudatum

Antioxidant drugs are actively used in medical practice for the treatment of inflammatory processes in various cardiac, ophthalmic, autoimmune, cancer and other diseases. The use of nanobiotechnological methods is a promising area of modern pharmacy, as it allows for creation of drugs of a qualitatively new level. Encapsulation of active pharmaceutical ingredients in liposomal nanoparticles makes it possible to increase the bioavailability and efficacy of natural antioxidants, to create water-soluble injectable forms of hydrophobic compounds. Biotesting is a simple, informative and rapid method to evaluate the toxicity and antioxidant activity of drugs, which can be a valid alternative to the use of laboratory ani­mals at the screening stage. Paramecium caudatum is an unicellular infusoria widely used as test-object due to high sensitivity to environmental changes; big cell size, which makes it possible to monitor changes in morphology and mobility of the cells; easy cultivation. The aim of the study is to evaluate the toxicity and antioxidant activity of liposomal forms of antioxidants: quercetin, curcumin, coenzyme Q10 and cytochrome C by biotesting method using Paramecium caudatum. The toxicity of liposomal forms of quercetin, curcumin, coenzyme Q10 and cytochrome C at doses of 25–100 μg/ml using Paramecium caudatum was studied. Incubation of Paramecium caudatum with liposomal forms of quercetin, curcumin and coenzyme Q10 led to growth of the cell culture, whereas liposomal cytochrome C caused cell lysis within 24 hours. It is established that toxicity of liposomal preparation is influenced by its lipid composition. Incorporation of anionic phospholipid (dipalmitoylphosphatidylglycerol) in lipid membrane significantly reduces the survival of the test culture compared with liposomes containing only phosphatidylcholine. In the model of oxidative stress induced in Paramecium caudatum by hydrogen peroxide, liposomal forms of quercetin, curcumin and coenzyme Q10 demonstrated dose-dependent antioxidant effects, which resulted in tole­rance increasing of the test culture to the toxicant.

A new perspective on the beryllium sensor platform: Low symmetry phthalocyanine-based molecular design and ultra trace amount Be2+ ion recognition in aqueous media

New multichannel sensors based on unsymmetrical phthalocyanines (P—A3BZnPc (1) and its water-soluble form Q—A3BZnPc (2)) were developed for Be2+ determination in water and THF. The structures of the sensors were elucidated by single-crystal X-ray diffraction and spectroscopic methods such as 1H- and 13C-NMR, IR, MALDI-TOF-MS, UV–vis, and steady-state fluorescence. The sensors (1) and (2) are dual-channel sensors and operate in the NIR region with λabs-λemm wavelengths of 685 nm –702 nm and 690 nm–706 nm, respectively. The selectivity of the sensors against Be2+ was explored in the presence of different metal ions (Li+, Na+, K+, Cs+, Mg2+, Ca2+, Ba2+, Al3+, Hg2+, Ni2+, Cd2+, Zn2+, Fe2+, Co2+, and Fe3+) and no significant interference was reported except Co2+, causing an interference only for sensor (2). Limit of Detection (LOD) measurements gave LOD values around 2.9 ppb, which is lower as compared to the threshold value in aqueous solution (4 ppb), determined by the World Health Organization (WHO). The response times of the sensors, estimated by UV–vis and fluorescence spectroscopy techniques, were found to be 0.7 s and 0.6 s, respectively. Owing to these short response times, the sensors can be included in the class of fast sensors when compared with other sensors given in the literature. The results prominently indicate that the sensors developed in this work are highly selective and sensitive to Be2+ and have a potential of usage in the detection of Be2+ in aqueous media.

Трансформация гидрофобных флавоноидов катехина, дигидрокверцетина и кверцетина в водорастворимые структуры

The paper describes methods for the transformation of poorly water-soluble flavonoids: dihydroquercetin, catechin and quercetin into water-soluble forms during the formation of supromolecular adducts with β-cyclodextrin and salt-type ionic complexes with the natural amino acid L-arginine, which contains a guanidine moiety properties necessary to create a cationic structure when interacting with phenolic groups. First, a methodology was developed for the synthesis of supromolecular structures, in which flavonoids were incorporated into a cyclodextrin matrix. As a result, the solubility in water at 20 °C of encapsulated flavonoids increased by more than two orders of magnitude. In the formation of complexes of cyclodextrin with flavonoids, the main role is played not by hydrogen bonds between the hydroxyl groups of flavonoids and β-cyclodextrin - in the case of dihydroquercetin and catechin, they are different and similar in the case of dihydroquercetin and quercetin, but the spatial orientation of the pyrocatechol cycle B (due to the flat conjugation of the entire molecule and due to sp2 is the structure of the second carbon atom of the pyran ring). Another implemented approach for obtaining water-soluble flavonoids at room temperature is the creation of their salts with the natural amino acid L-arginine, which is a part of proteins and is involved in several vital processes in the body. The structure of the obtained compounds was proved by the methods of NMR spectroscopy on 13C nuclei and X-ray structural analysis, the composition – by elemental analysis.

HYPERACCUMULATOR PLANTS FOR PHYTOREMEDIATION OF SOIL CONTAMINATED WITH HEAVY METALS

Environmental pollution, including pollution of urban soils by heavy metals causes serious environmental concern around the world. Heavy metals accumulate relatively quickly in soil but their removal rate is very slow. Hyperaccumulator plants help cleanse the environment from heavy metals. Phytoremediation is cleansing of soils contaminated with heavy metals, using plants that accumulate significant amounts of metals. An important environmental problem in large industrial cities is pollution by toxic compounds, including heavy metals. Due to the potential toxicity and high resistance of metals, soils contaminated with these elements are an environmental problem that requires effective and affordable solution. In soils heavy metals are in varying degrees of accessibility to plants. Water-soluble forms of heavy metals, as a rule, are presented in the form of various salts and organic complex compounds. Phytoremediation of urban soils from heavy metals is an important environmental challenge. Among the wild species, a special group of heavy metal hyperaccumulator plants is highlighted. Some of the land plants that can accumulate abnormally high levels of potentially toxic trace elements are known as “hyperaccumulators” and their number includes about 500 taxa. Phytoremediation is much more environmentally friendly and cheaper than other techniques, so recently it has received widespread use in various countries.

Water Extracts as Criterion of Assessment of Geochemical Conditions on a Monolithic Soil–Geochemical Catena in the Upper Reaches of the Klyaz’ma River

The composition of water-soluble macro- and microelements and anions has been studied in soils formed within a monolithic soil–geochemical catena. It has been shown that the carbon and nitrogen contents regularly increase from eluvial to accumulative landscapes parallel to their hydromorphism. The distribution of water-soluble forms of macro- and microelements is related to bioaccumulative processes and features of eluvial–illuvial differentiation of soils. The margins of the watershed depression are characterized by the combination of eluvial–illuvial differentiation and intensive lateral removal of elements in spring, which determines the maximal leaching of the top soil horizons. The data of the cluster analysis confirm that there is a correlation of soil genesis and location in the system of geochemical catena with the composition of water extracts.

Simultaneous fortification of rice with folic acid and β-carotene or vitamin A by limited-water parboiling

Rice fortification by parboiling has been used to fortify rice with a single or a combination of multiple nutrients. While several studies have demonstrated the success of rice fortification with minerals by the parboiling technique, the number of studies that used vitamins as fortificants is limited with varying results. A limited-water soaking method has been introduced as a feasible and more sustainable alternative to the conventional excess-water soaking in parboiling. This study investigated the application of limited-water soaking in the simultaneous fortification of rice with water- and fat-soluble vitamins. Pure and water-soluble forms of β-carotene and vitamin A were first compared to identify a more effective form to be combined with folic acid. Water-soluble forms of β-carotene and vitamin A were easy to incorporate into the soaking water and presented effective fortification without affecting rice milling quality, the amount of wastewater and solids in wastewater. Milled rice fortified with folic acid combined with water-soluble forms of β-carotene or vitamin A in the limited-water soaking method contributed to about 75% of the recommended dietary allowances (RDAs) for folic acid, about 173% (female) and 134% (male) of the RDAs for β-carotene, and to about 58% (female) and 45% (male) of the RDAs for vitamin A. Rice fortified with β-carotene showed a greater uptake and a more orange color compared to the others. Thus, fortification of rice with vitamins by limited-water parboiling is an efficient process to obtain fortified rice that can significantly increase vitamin intake with limited environmental impacts.

Nicotinamide restricts neural precursor proliferation to enhance catecholaminergic neuronal subtype differentiation from mouse embryonic stem cells.

Emerging evidence indicates that a strong relationship exists between brain regenerative therapies and nutrition. Early life nutrition plays an important role during embryonic brain development, and there are clear consequences to an imbalance in nutritional factors on both the production and survival of mature neuronal populations and the infant’s risk of diseases in later life. Our research and that of others suggest that vitamins play a fundamental role in the formation of neurons and their survival. There is a growing body of evidence that nicotinamide, the water-soluble amide form of vitamin B3, is implicated in the conversion of pluripotent stem cells to clinically relevant cells for regenerative therapies. This study investigated the ability of nicotinamide to promote the development of mature catecholaminergic neuronal populations (associated with Parkinson’s disease) from mouse embryonic stem cells, as well as investigating the underlying mechanisms of nicotinamide’s action. Nicotinamide selectively enhanced the production of tyrosine hydroxylase-expressing neurons and serotonergic neurons from mouse embryonic stem cell cultures (Sox1GFP knock-in 46C cell line). A 5-Ethynyl-2´-deoxyuridine (EdU) assay ascertained that nicotinamide, when added in the initial phase, reduced cell proliferation. Nicotinamide drove tyrosine hydroxylase-expressing neuron differentiation as effectively as an established cocktail of signalling factors, reducing the proliferation of neural progenitors and accelerating neuronal maturation, neurite outgrowth and neurotransmitter expression. These novel findings show that nicotinamide enhanced and enriched catecholaminergic differentiation and inhibited cell proliferation by directing cell cycle arrest in mouse embryonic stem cell cultures, thus driving a critical neural proliferation-to-differentiation switch from neural progenitors to neurons. Further research into the role of vitamin metabolites in embryogenesis will significantly advance cell-based regenerative medicine, and help realize their role as crucial developmental signalling molecules in brain development.

Photooxidative stress-inducible orange and pink water-soluble astaxanthin-binding proteins in eukaryotic microalga

Lipid astaxanthin, a potent antioxidant known as a natural sunscreen, accumulates in eukaryotic microalgae and confers photoprotection. We previously identified a photooxidative stress-inducible water-soluble astaxanthin-binding carotenoprotein (AstaP) in a eukaryotic microalga (Coelastrella astaxanthina Ki-4) isolated from an extreme environment. The distribution in eukaryotic microalgae remains unknown. Here we identified three novel AstaP orthologs in a eukaryotic microalga, Scenedesmus sp. Oki-4N. The purified proteins, named AstaP-orange2, AstaP-pink1, and AstaP-pink2, were identified as secreted fasciclin proteins with potent 1O2 quenching activity in aqueous solution, which are characteristics shared with Ki-4 AstaP. Nonetheless, the absence of glycosylation in the AstaP-pinks, the presence of a glycosylphosphatidylinositol (GPI) anchor motif in AstaP-orange2, and highly acidic isoelectric points (pI = 3.6–4.7), differed significantly from that of AstaP-orange1 (pI = 10.5). These results provide unique examples on the use of water-soluble forms of astaxanthin in photosynthetic organisms as novel strategies for protecting single cells against severe photooxidative stresses.

La, Ce and Nd in the soil-plant system in a vegetation experiment with barley (Hordeum vulgare L.)

Rare earth elements (REEs) have received enormous attention in recent years. However, there are many gaps in the understanding of their behavior in the soil-plant system. The aim of this study is to investigate the behavior of three most common REEs (La, Ce, Nd) in the soil-plant system directly on soil samples using barley (Hordeum vulgare L.) in a vegetation experiment. We attribute the absence of significant changes in plant biomass and photosynthetic pigment content to the reduced availability of REEs in soil samples. The concentration of water-soluble forms of La, Ce and Nd didn't exceed 1 mg/kg, while the concentration of exchangeable forms varied and decreased in a row La > Ce > Nd. The transfer factor (TF) from soil to above-ground biomass was low for all three elements (<1). The stem-to-leaf TF increased with the increase in REEs concentration in soil. The concentration in plant material increased in the row Ce < Nd < La. REEs concentrations in barley leaves didn't exceed 1–3% of the corresponding element concentration in soil samples. REEs concentration in plant tissues is in close direct correlation with the REEs total concentration in soil, water-soluble and exchange forms. REEs concentration in barley leaves is 3–4 times higher than in the stems and for the group with extraneous concentration of 200 mg/kg for La, Ce and Nd was 6.20 ± 1.48, 2.10 ± 0.51, 6.90 ± 3.00 mg/kg, respectively. We show that there were no major changes in barley plants, but further study is needed of the relationship between the absorption of lanthanides by plants and the content of various forms of lanthanides in the soil.

Synthesis of water-soluble zinc(ii) nitrilotris(methylenephosphonate). Molecular structure of bis(4-carboxyphenylaminium) nitrilotris(methylenephosphonate) dihydrate

Nitrilotris(methylenephosphonic)acid N[CH2P(O)(OH)2]3 (H6L) reacts with zinc oxide in an aqueous medium to give a poorly soluble polymeric crystalline salt (ZnH4L)n. The reaction proceeds through the intermediate formation of a soluble monomer complex ZnH4L. The water-soluble amorphous forms of the coordination compound used as microfertilizers were obtained by treatment of a suspension of this salt with 2-aminoethanol, 2-amino-2-(hydroxymethyl)propane-1,3-diol, 2,2′-(ethylenedioxy)bis(ethylamine). p-Aminobenzoic acid H2NC6H4COOH reacts in an aqueous solution with hexabasic nitrilotrimethylenephosphonic acid, as well as with the monomeric complex ZnH4L, giving crystals of bis(4-carboxyphenylaminium) nitrilotris(methylenephosphonate) dihydrate H4L2− · 2(H3N-C6H4-COOH)+ · 2H2O. The compounds were investigated by elemental analysis, IR and UV spectroscopy, X-ray phase analysis and X-ray diffraction analysis. Tests of the water-soluble complex with 2-aminoethanol ZnHL3− · 3(H3NCH2CH2OH)+ · 2H2O in the laboratory experiment with seeds of two agricultural crops showed a positive agronomic effect.

Improved antileishmanial activity and cytotoxicity of a novel nanotherapy for N-iodomethyl-N,N-dimethyl-N-(6,6-diphenylhex-5-en-1-yl)ammonium iodide

The N-iodomethyl-N, N-Dimethyl-N-(6,6-diphenylhex-5-en-1-yl) ammonium iodide (C6I) is a new chemical entity (NCE) with demonstrated in vitro and in vivo antileishmanial activity. As many others NCE, C6I is poorly water soluble (Class II of the Biopharmaceutical Classification System), thus its oral administration is potentially compromised. To overcome the issue, nanotechnology is a real and useful tool. Moreover, nanotechnology can improve C6I internalization by macrophages, the drug targets, therefore increasing its antileishmanial activity.The present work aimed to develop a potential suitable oral nanodrug delivery system for C6I to improve its antileishmanial activity. For this purpose, polymeric and solid lipid nanoparticles were developed. Polylactic-co-glycolic acid polyester (PLGA) were prepared by nanoprecipitation while solid lipid nanoparticles made of glycerol tripalmitate (Trp) and glyceryl tristearate (Trs) were obtained by emulsion–solvent evaporation method. Physicochemical characterization of all formulations was performed, as well as stability studies. A lyophilization procedure was also established. Biological activity was evaluated by antileishmanial activity and cytotoxicity in vitro assays.Five types of commercial PLGA to encapsulate C6I were tested. The best results were obtained using PLGA 752S and d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS), the water-soluble form of vitamin E. Particles around 220 nm in diameter and encapsulation efficiency (EE) up to 60% were obtained. Solid lipid nanoparticles based on Trs and Trp lipids were also in the nanoscale showing a low polydispersity index and EE% >60%. Both types of nanoformulations, polymeric and lipidic, thd C6I cytotoxicity in human and hamster macrophages cell cultures. In vitro assays with PLGA loaded-C6I showed a noticeable improved antileishmanial activity on intracellular amastigotes of L. (V.) panamensis, with the following EC50 values: PLGA «< Trs-SLN « free C6I < Trp-SLN. In conclusion, PLGA nanoformulation could be a suitable candidate for preclinical evaluation in animal model.

Computational design of transmembrane pores.

Protein pores play key roles in fundamental biological processes1 and biotechnological applications such as DNA nanopore sequencing2–4, and hence the design of pore-containing proteins is of considerable scientific and biotechnological interest. Synthetic amphiphilic peptides have been found to form ion channels5,6, and there have been recent advances in de novo membrane protein design7,8 and in redesigning naturally occurring channel-containing proteins9,10. However, the de novo design of stable, well-defined transmembrane protein pores capable of conducting ions selectively or large enough to allow passage of small-molecule fluorophores remains an outstanding challenge11,12. Here, we report the computational design of protein pores formed by two concentric rings of ɑ-helices that are stable and mono-disperse in both water-soluble and transmembrane forms. Crystal structures of the water-soluble forms of a 12 helical and a 16 helical pore are close to the computational design models. Patch-clamp electrophysiology experiments show that the transmembrane form of the 12-helix pore expressed in insect cells allows passage of ions across the membrane with high selectivity for potassium over sodium, which is blocked by specific chemical modification at the pore entrance. The transmembrane form of the 16-helix pore, but not the 12-helix pore, allows passage of biotinylated Alexa Fluor 488 when incorporated into liposomes using in vitro protein synthesis. A cryo-EM structure of the 16-helix transmembrane pore closely matches the design model. The ability to produce structurally and functionally well-defined transmembrane pores opens the door to the creation of designer pores for a wide variety of applications.

Andrographolide sulfate inhibited NF-κB activation and alleviated pneumonia induced by poly I:C in mice

Pneumonia is a common illness that continues to be the major killer of remaining to be a significant source of morbidity and mortality in the patient population. Many microorganisms cause pneumonia, and now concern is turning to the importance of the cause the new therapies for viral pneumonia. In the current study, we report the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on poly I: C-induced pneumonia. Andrographolide sulfonate was administrated through intraperitoneal injection to mice with poly I: C-induced pneumonia. Recruitment of airway inflammatory cells, alteration of lung histological induced by Poly I: C were significantly ameliorated by andrographolide sulfonate. The protein levels of pro-inflammatory cytokines in bronchoalveolar fluid (BALF) and serum were reduced by andrographolide sulfonate treatment. The levels of MUC5AC and MUC5B in lung tissue were also suppressed. These results reveal that andrographolide sulfate remarkably alleviated pneumonia induced by poly I:C in mice. Moreover, andrographolide sulfonate markedly inhibited the activation of nuclear factor-κB (NF-κB). Taken together, we demonstrated that andrographolide sulfonate ameliorated poly I: C-induced pneumonia in mice, suggesting the possible use of andrographolide sulfonate for virus-induced pneumonia in clinical.