Berberine potently inhibits protein tyrosine phosphatase 1B: investigation by docking simulation and experimental validation

Berberine was investigated as an inhibitor of human protein tyrosine phosphatase 1B (h-PTP 1B) in an attempt to explain its anti-hyperglycemic activitiy. The investigation included simulated docking experiments to fit berberine within the binding pocket of h-PTP 1B. Berberine was found to readily fit within the binding pocket of h-PTP 1B in a low energy orientation characterized with optimal electrostatic attractive interactions bridging the isoquinolinium positively charged nitrogen atom of berberine and the negatively charged acidic residue of ASP 48 of h-PTP 1B. Experimentally, berberine was found to potently competitively inhibit recombinant h-PTP 1B in vitro (Ki value = 91.3 nM). Our findings strongly suggest that h-PTP 1B inhibition is at least one of the reasons for the reported anti-hyperglycemic activities of berberine.     

Synthesis and antiviral activity of some C2-, C4-, and C6-substituted pyrazolo[3,4-D]pyrimidine acyclonucleosides with the alkylating chains of ACV, HBG, and ISO-DHPG

A useful route to obtain trisubstituted pyrazolo[3,4-d]pyrimidines 14-17 is described. Those later were coupled with the alkylating agents 18-20 as in ACV, HBG, and iso-DHPG to give, after deprotection, the desired acylonucleosides 33-44. Almost all of the new compounds were evaluated for their inhibitory effects against the replication of various DNA viruses in culture.     

Oxidized LDL immune complexes induce release of sphingosine kinase in human U937 monocytic cells

The transformation of macrophages into foam cells is a critical event in the development of atherosclerosis. The most studied aspect of this process is the uptake of modified LDL through the scavenger receptors. Another salient aspect is the effect of modified LDL immune complexes on macrophages activation and foam cell formation. Macrophages internalize oxidized LDL immune complexes (oxLDL-IC) via the Fc-gamma receptor and transform into activated foam cells. In this study we examined the effect of oxLDL-IC on sphingosine kinase 1 (SK1), an enzyme implicated in mediating pro-survival and inflammatory responses through the generation of the signaling molecule sphingosine-1-phosphate (S1P). Intriguingly, oxLDL-IC, but not oxLDL alone, induced an immediate translocation and release of SK1 into the conditioned medium as evidenced by fluorescence confocal microscopy. Immunoblot analysis of cell lysates and conditioned medium revealed a decrease in intracellular SK1 protein levels accompanied by a concomitant increase in extracellular SK1 levels. Furthermore, measurement of S1P formation showed that the activity of cell-associated SK decreased in response to oxLDL-IC compared to oxLDL alone, whereas the activity of SK increased extracellularly. Blocking oxLDL-IC binding to Fc-gamma receptors resulted in decreased levels of extracellular S1P. The data also show that cell survival of human U937 cells exposed to oxLDL-IC increased compared to oxLDL alone. Exogenously added S1P further increased cell survival induced by oxLDL-IC. Taken together, these findings indicate that S1P may be generated extracellularly in response to modified LDL immune complexes and may therefore promote cell survival and prolong cytokine release by activated macrophages.     

Nor-ent-kaurane diterpenes and hydroxylactones from Antennaria geyeri and Anaphalis margaritacea

In a study of Pacific Northwest plants of the Asteraceae family, a nor-ent-kaurane diterpene and a known diterpene, both displaying antibacterial activities, were isolated together with scopoletin and sitosterol-3-O-beta-glucopyranoside from the aerial parts of Antennaria geyeri. Anaphalis margaritacea afforded two hydroxylactones. The structures were established by one and two dimensional NMR techniques, IR and CIMS.     

Bacterial Diversity and Sulfur Cycling in a Mesophilic Sulfide-Rich Spring

An artesian sulfide- and sulfur-rich spring in southwestern Oklahoma is shown to sustain an extremely rich and diverse microbial community. Laboratory incubations and autoradiography studies indicated that active sulfur cycling is occurring in the abundant microbial mats at Zodletone spring. Anoxygenic phototrophic bacteria oxidize sulfide to sulfate, which is reduced by sulfate-reducing bacterial populations. The microbial community at Zodletone spring was analyzed by cloning and sequencing 16S rRNA genes. A large fraction (83%) of the microbial mat clones belong to sulfur- and sulfate-reducing lineages within δ-Proteobacteria, purple sulfur γ-Proteobacteria, -Proteobacteria, Chloroflexi, and filamentous Cyanobacteria of the order Oscillatoria as well as a novel group within γ-Proteobacteria. The 16S clone library constructed from hydrocarbon-exposed sediments at the source of the spring had a higher diversity than the mat clone library (Shannon-Weiner index of 3.84 compared to 2.95 for the mat), with a higher percentage of clones belonging to nonphototrophic lineages (e.g., Cytophaga, Spirochaetes, Planctomycetes, Firmicutes, and Verrucomicrobiae). Many of these clones were closely related to clones retrieved from hydrocarbon-contaminated environments and anaerobic hydrocarbon-degrading enrichments. In addition, 18 of the source clones did not cluster with any of the previously described microbial divisions. These 18 clones, together with previously published or database-deposited related sequences retrieved from a wide variety of environments, could be clustered into at least four novel candidate divisions. The sulfate-reducing community at Zodletone spring was characterized by cloning and sequencing a 1.9-kb fragment of the dissimilatory sulfite reductase (DSR) gene. DSR clones belonged to the Desulfococcus-Desulfosarcina-Desulfonema group, Desulfobacter group, and Desulfovibrio group as well as to a deeply branched group in the DSR tree with no representatives from cultures. Overall, this work expands the division-level diversity of the bacterial domain and highlights the complexity of microbial communities involved in sulfur cycling in mesophilic microbial mats.     

Synthesis and biological evaluation of some acyclic 4,6-disubstituted 1H-pyrazolo[3,4-d]pyrimidine nucleosides

The chemical synthesis and biological evaluation of some acyclic alpha-[6-(1'-carbamoylalkylthio)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]thioalkylamide nucleosides are described.     

Goitrogenic activity of p-coumaric acid in rats

The effects of three natural phenolic acids (caffeic, ferulic, and p-coumaric) on the rat thyroid gland were examined in a 3-week oral-treatment study. Forty male Wistar albino rats, divided into groups of 10 rats each and fed iodine-rich diet, were administered by gastrointestinal tube saline (control), caffeic acid, ferulic acid, or p-coumaric acid at a dose level of 0.25 micromol/kg/day for 3 weeks. The mean absolute and relative thyroid weights in caffeic, ferulic, or p-coumaric acid groups were significantly increased to 127 and 132%, 146 and 153%, or 189 and 201% compared to control value, respectively. Histological examination of the thyroids of p-coumaric acid group revealed marked hypertrophy and/or hyperplasia of the follicles. Caffeic or ferulic groups showed slight to moderate thyroid gland enlargement. Thyroid lesions in p-coumaric acid group were associated with significant increases in cellular proliferation as indicated by [(3)H]thymidine incorporation. In addition, the goitrogenic effect of p-coumaric acid was further confirmed by significant decreases (50%) in serum tri-iodothyronine (T(3)) and thyroxine (T(4)), and a parallel increase (90%) in serum thyroid stimulating hormone (TSH) compared to control group. These results indicate that administration of p-coumaric acid at relatively high doses induces goiter in rats.     

Recent trends using natural polymeric nanofibers as supports for enzyme immobilization and catalysis

All the disciplines of science, especially biotechnology, have given continuous attention to the area of enzyme immobilization. However, the structural support made by material science intervention determines the performance of immobilized enzymes. Studies have proven that nanostructured supports can maintain better catalytic performance and improve immobilization efficiency. The recent trends in the application of nanofibers using natural polymers for enzyme immobilization have been addressed in this review article. A comprehensive survey about the immobilization strategies and their characteristics are highlighted. The natural polymers, e.g., chitin, chitosan, silk fibroin, gelatin, cellulose, and their blends with other synthetic polymers capable of immobilizing enzymes in their 1D nanofibrous form, are discussed. The multiple applications of enzymes immobilized on nanofibers in biocatalysis, biosensors, biofuels, antifouling, regenerative medicine, biomolecule degradation, etc.; some of these are discussed in this review article.     

Salmonella species isolated from animal feed in Iraq.

Of 700 animal feed samples, 32 (4.5%) harbored Salmonella. The highest percentage of contamination was found in sheep feed and local protein. A total of 17 Salmonella serotypes were identified. The most frequent serotypes were Salmonella meleagridis. S. bornum, S. montevideo, and S. drypool. S. bornum was isolated for the first time in Iraq and from both local feed and its ingredients. The common somatic group found was that of Salmonella group C; then came groups E, G, B, and D. Three serotypes (S. enteritidis, S. california, and S. muenchen) seemed to form a link of infection among feed, food, patients, and carriers.