Hydroferrate Fluid,MRN-100, Provides Protection against Chemical-Induced Gastric and Esophageal Cancer in Wistar Rats

In the current study, we examined the protective effect of hydroferrate fluid MRN-100 against the carcinogen methylnitronitrosoguanidine (MNNG)-induced gastric and esophageal cancer in rats. MRN-100 is an iron-based compound composed of bivalent and trivalent ferrates. At 33 weeks post treatment with MNNG, rats were killed and examined for the histopathology of esophagus and stomach; liver, spleen, and total body weight; and antioxidant levels in the blood and stomach tissues. Results showed that 17/20 (85%) gastroesophageal tissues from carcinogen MNNG-treated rats developed dysplasia and cancer, as compared to 8/20 (40%) rats treated with MNNG plus MRN-100. In addition, MRN-100 exerted an antioxidant effect in both the blood and stomach tissues by increasing levels of GSH, antioxidant enzymes SOD, CAT, and GPx, and total antioxidant capacity (TAC) level. This was accompanied by a reduction in the total free-radical and malondialdehyde levels. Furthermore, MRN-100 protected against body and organ weight loss. Thus, MRN-100 exhibited significant cancer chemopreventive activity by protecting tissues against oxidative damage in rats, which may suggest its effectiveness as an adjuvant for the treatment of gastric/esophageal carcinoma.     

Physical and chemical characteristics of the Blue Nile and the White Nile at Khartoum

Fortnightly measurements of physical and chemical variables were made at two locations on the Blue and White Niles near Khartoum from August 1968 to December 1970. Variables analysed from each river were: temperature, pH, total residue, current velocity, oxygen, alkalinity, phosphate, nitrate, ammonia, silica, sulphate, iron, calcium, magnesium, sodium, potassium and oxidizable organic matter. The seasonal variations of these factors in the two Niles are compared and the interrelationships existing between some of them are discussed. Comparisons with earlier studies on the Nile and with some tropical rivers are made.In the Blue Nile, the amounts of suspended matter and nutrients are largely dependent upon the flood regime. Nitrate, phosphate, iron, oxidizable organic matter and total residue increase considerably in the Blue Nile when the river is in flood (peaks: 1 880 µg NO₃-N l^–1; 0.31 mg Fe l^–1; 3 842 mg total residue · l^–1).In the White Nile, concentrations of nitrate, phosphate, iron, oxidizable organic matter and total residue attain their peaks during the rainy season (270 µg NO₃-N l^–1; 163 tag PO₄-P l^–1; 0.46 mg Fe · l^–1; 502 mg total residue · l^–1).In both rivers, alkalinity, calcium, sodium and potassium tend to increase during the dry season while declining in the rainy season. Silica is depleted at certain times of the year, yet relatively high concentrations are maintained throughout the year and were not expected to limit growth of diatoms. Fall in silica concentrations, unlike nitrate, phosphate and iron, was always followed by a rapid restoration of a high level. Silica and magnesium showed no response to changes in discharge rates.     

Toxicity in Tilapia zilli and Clarias lazera (Pisces) induced by zinc, seasonally

Subadult teleosts, Tilapia zilli and Clarias lazera, were exposed in laboratory bioassays to lethal and sublethal concentrations of zinc, seasonally (at range of temperature between 9.3 +/- 1.5 and 25 +/- 1 degree C). It appears that Tilapia is more susceptible to Zn than Clarias and both species are more resistant to Zn toxicity at lower temperature (during winter). To determine the uptake and tissue distribution of Zn in the two species, gill, liver and muscles were analysed at moderate temperature (during spring). After a 96 hr exposure period, Zn was decreased in the following order: gill greater than liver greater than muscle.     

Growth and ion uptake by maize seedlings on solutions variable in calcium and flow rate

Summary Growth and ion uptake by maize seedlings was studied as functions of calcium concentration and rate of flow of nutrient solutions. With calcium concentrations established at 1, 10, and 100 ppm Ca, all other nutrients being kept at constant concentration, the solutions passed through narrow culture trays at velocities of 2, 8, and 24 liter/day.Fresh and dry weights of seedlings increased as the concentration of calcium increased from 1 to 10 or 100 ppm for any value ofV.Positive response in the plant calcium content was particularly noticed when Ca increased to 100 ppm in the nutrient solution. Phosphorus content of tops decreased with increasing (Ca) in the nutrient solution, while the other elements were more or less unaffected. In the case of roots, phosphorus was generally increased, iron decreased and potassium showed inconsistent trends.Estimates of the uptake efficiency relative to calcium were made by calculating the ratio of the amount of calcium taken up by the entire seedling to the product of calcium concentration and daily flow rate of the solution. It appears that the uptake efficiency diminishes with increasing flow rate. Other instances points to the maintenance of the same uptake efficiency as (Ca) increased with the decreasingV or vice versa. These observations point to the critical nature of environmental factors on the effective contacts between supply and uptake belts that have been adopted as model in this study.     

Extracellular vesicles released from the filarial parasite Brugia malayi downregulate the host mTOR pathway

We have previously shown that the microfilarial (mf) stage of Brugia malayi can inhibit the mammalian target of rapamycin (mTOR; a conserved serine/threonine kinase critical for immune regulation and cellular growth) in human dendritic cells (DC) and we have proposed that this mTOR inhibition is associated with the DC dysfunction seen in filarial infections. Extracellular vesicles (EVs) contain many proteins and nucleic acids including microRNAs (miRNAs) that might affect a variety of intracellular pathways. Thus, EVs secreted from mf may elucidate the mechanism by which the parasite is able to modulate the host immune response during infection. EVs, purified from mf of Brugia malayi and confirmed by size through nanoparticle tracking analysis, were assessed by miRNA microarrays (accession number {"type":"entrez-geo","attrs":{"text":"GSE157226","term_id":"157226"}}GSE157226) and shown to be enriched (>2-fold, p-value<0.05, FDR = 0.05) for miR100, miR71, miR34, and miR7. The microarray analysis compared mf-derived EVs and mf supernatant. After confirming their presence in EVs using qPCR for these miRNA targets, web-based target predictions (using MIRPathv3, TarBAse and MicroT-CD) predicted that miR100 targeted mTOR and its downstream regulatory protein 4E-BP1. Our previous data with live parasites demonstrated that mf downregulate the phosphorylation of mTOR and its downstream effectors. Additionally, our proteomic analysis of the mf-derived EVs revealed the presence of proteins commonly found in these vesicles (data are available via ProteomeXchange with identifier PXD021844). We confirmed internalization of mf-derived EVs by human DCs and monocytes using confocal microscopy and flow cytometry, and further demonstrated through flow cytometry, that mf-derived EVs downregulate the phosphorylation of mTOR in human monocytes (THP-1 cells) to the same degree that rapamycin (a known mTOR inhibitor) does. Our data collectively suggest that mf release EVs that interact with host cells, such as DC, to modulate host responses.     

Acyclo C-Nucleoside Analogs. Regioselective Annellation of a Triazole Ring to 5-Methyl-1,2,4-Triazino[5,6-b]Indole and Formation of Certain 3-Poly Hydroxyalkyl Derivatives

ABSTRACT

Cyclodehydrogenation of the ethylidene derivative of (5-methyl-1,2,4-triazino[5,6-b]indol-3-yl)hydrazine (1) gave the angular isomer, 1,10-dimethyl-1,2,4-triazolo[3′,4′:3,4][1,2,4]triazino[5,6-b]indole (4). The linear isomer, 3,10-dimethyl-1,2,4-triazolo[4′,3′:2,3][1,2,4]triazino[5,6-b]indole (7) could be prepared regioselectively by the cyclodehydration of the acetyl derivative of 1. The cyclodehydrogenation was extended to the monosaccharide derivatives of 1. The role of the N-methyl group on the site of annellation has been discussed.     

Pepsin as a catalyst of peptide synthesis. Enzyme co-precipitation with emerging peptide products.

Pepsin successfully catalyzed the synthesis of several peptide derivatives from N-protected di- or tripeptides and amino acid or peptide esters or p-nitroanilides in dimethylformamide-water solutions at pH 4.6. An optimal substrates:pepsin ratio depended on the structure of starting peptides, especially their fit to the substrate binding sites of the enzyme. For hexapeptide Z-Ala-Ala-Phe-Leu-Ala-Ala-OCH3 formation, an equilibrium yield was attained at 1:3.10(5) enzyme-substrates ratio that indicated high efficiency of pepsin in synthesis reactions. In the course of the equilibrium peptide synthesis, pepsin gradually disappeared from the liquid phase due to its entrapment within a gel, formed by the hexapeptide product, while retaining its activity. The inclusion into the precipitate was not specific for pepsin, so far as inert proteins, lysozyme, ribonuclease A and carbonic anhydrase, when added to the reaction mixture, became also co-precipitated with the hexapeptide formed. It appears that co-precipitation of pepsin, an important factor limiting the enzyme efficiency, might be operative as well for other proteinases used to catalyze peptide synthesis.     

A carotane derivative and a eudesmanolide from Inula crithmoides*

The aerial parts of Inula crithmoides afforded a new carotane derivative and a eudesmanolide, inucrithmolide. The most probable structures were elucidated by the spectroscopic data and by some chemical transformations.