Rutin modulates ASC expression in NLRP3 inflammasome: a study in alcohol and cerulein-induced rat model of pancreatitis

Inflammasomes are protein complexes formed in response to tissue injury and inflammation to regulate the formation of proinflammatory cytokines. Nod-like receptor pyrin domain containing 3 (NLRP3) is one such inflammasome involved in pancreatic inflammation. Caspase activation recruitment domain (CARD) is an interaction motif found in all the major components of NLRP3 inflammasome such as apoptosis associated speck-like CARD containing protein (ASC) and procaspase-1. NLRP3 activates procaspase-1 with the concerted action of CARD domain of ASC. In the present study, the effect of rutin, a natural flavonoid on the expression of ASC of NLRP3, was investigated in rats treated with ethanol (EtOH) and cerulein (Cer). Male albino Wistar rats were divided into four groups. Groups 1 and 2 rats were fed normal diet, whereas groups 3 and 4 rats were fed EtOH (36 % of total calories) containing diet for a total period of 5 weeks and also administered Cer (20 µg/kg body weight i.p.) thrice weekly for the last 3 weeks. In addition, groups 2 and 4 rats received daily 100 mg/kg body weight of rutin from third week. Rutin co-administration significantly decreased the level of pancreatic marker enzymes, oxidative stress markers, inflammatory markers, mRNA expression of caspase-1, cytokines, ASC–NLRP3, and protein expression of caspase-1 and ASC in rats received EtOH–Cer. The results of the study revealed that rutin can reduce inflammation in pancreas probably by influencing the down regulation of ASC–NLRP3 which might result in the reduced activation of caspase-1 and controlled cytokine production.     

Serotype-conversion in Shigella flexneri: identification of a novel bacteriophage,Sf101, from a serotype 7a strain

Background

Shigella flexneri is the major cause of bacillary dysentery in the developing countries. The lipopolysaccharide (LPS) O-antigen of S. flexneri plays an important role in its pathogenesis and also divides S. flexneri into 19 serotypes. All the serotypes with an exception for serotype 6 share a common O-antigen backbone comprising of N-acetylglucosamine and three rhamnose residues. Different serotypes result from modification of the basic backbone conferred by phage-encoded glucosyltransferase and/or acetyltransferase genes, or plasmid-encoded phosphoethanolamine transferase. Recently, a new site for O-acetylation at positions 3 and 4 of Rha^III, in serotypes 1a, 1b, 2a, 5a and Y was shown to be mediated by the oacB gene. Additionally, this gene was shown to be carried by a transposon-like structure inserted upstream of the adrA region on the chromosome.

Results

In this study, a novel bacteriophage Sf101, encoding the oacB gene was isolated and characterised from a serotype 7a strain. The complete sequence of its 38,742 bp genome encoding 66 open reading frames (orfs) was determined. Comparative analysis revealed that phage Sf101 has a mosaic genome, and most of its proteins were >90% identical to the proteins from 12 previously characterised lambdoid phages. In addition, the organisation of Sf101 genes was found to be highly similar to bacteriophage Sf6. Analysis of the Sf101 OacB identified two amino acid substitutions in the protein; however, results obtained by NMR spectroscopy confirmed that Sf101-OacB was functional. Inspection of the chromosomal integration site of Sf101 phage revealed that this phage integrates in the sbcB locus, thus unveiling a new site for integration of serotype-converting phages of S. flexneri, and determining an alternative location of oacB gene in the chromosome. Furthermore, this study identified oacB gene in several serotype 7a isolates from various regions providing evidence of O-acetyl modification in serotype 7a.

Conclusions

This is the first report on the isolation of bacteriophage Sf101 which contains the S. flexneri O-antigen modification gene oacB. Sf101 has a highly mosaic genome and was found to integrate in the sbcB locus. These findings contribute an advance in our current knowledge of serotype converting phages of S. flexneri.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-742) contains supplementary material, which is available to authorized users.     

Effects of sequential depositional basins on lake response to urban and agricultural pollution: a palaeoecological analysis of the Qu'Appelle Valley, Saskatchewan, Canada

1. Palaeolimnological analyses of fossil diatoms and pigments were conducted in four lakes of the Qu'Appelle Valley, Saskatchewan, Canada, to quantify the effect of upstream depositional basins on lake response to urban and agricultural human activities. Pasqua, Echo, Mission and Katepwa lakes exhibit similar modern limnological characteristics, lie sequentially downstream from urban point sources of growth‐limiting nitrogen (N), yet drain similarly large areas of farmland (38–40 × 10³ km²). 2. Analyses indicated that all lakes were naturally productive, contained eutrophic diatoms (i.e. Stephanodiscus niagarae, S. hantzchii, S. parvus and Aulacoseira granulata), and supported blooms of colonial (as myxoxanthophyll) and potentially toxic N‐fixing cyanobacteria (aphanizophyll), even prior to the onset of European settlement (ca. 1890) and urban development (ca. 1930). 3. The onset of agricultural practices ca. 1890 had only modest effects on algal communities in the Qu'Appelle lakes, with subtle increases in eutrophic diatom species (Pasqua, Mission and Katepwa lakes) and 25–50% increases in pigment‐inferred algal abundance (Echo, Mission and Katepwa lakes). 4. Despite naturally high production, total algal abundance (β‐carotene) in upstream Pasqua Lake increased by more than 350% after intense urbanization beginning ca. 1930, while eutrophic diatoms became more common and cyanobacteria populations increased ten‐fold. Principal components analysis (PCA) explained 64% of diatom variance, and identified three eras corresponding to baseline, pre‐agricultural communities (1776–1890), an era of high production (ca. 1925–1960) and recent variable community composition following tertiary treatment of urban sewage (ca. 1977–1990). 5. Analyses of three downstream lakes demonstrated that urban impacts following 1930 remained evident in fossil profiles of β‐carotene and myxoxanthophyll, but that large blooms of N‐fixing cyanobacteria were restricted to the past 25 years at downstream Mission and Katepwa lakes. Similarly, PCA showed that fossil diatom assemblages exhibited little directional variation until the 1970s. 6. Together, these analyses support the hypothesis that upstream lakes were effective at reducing the impacts of point‐source urban nutrients on downstream lakes. In contrast, diffuse agricultural activities had only limited impacts on water quality and these were less well ameliorated by upstream basins.     

Long-term trends in limnological characteristics in the Aurora trout lakes, Sudbury, Canada

Paleolimnological techniques were employed to document the limnological histories of the aurora trout lakes, located in the Sudbury region of Ontario. Two of these lakes are of special interest to fisheries managers, as they represent the only known native habitats of a rare strain of brook trout: the aurora trout. These lakes were limed as part of restoration efforts. Stratigraphic changes in diatom and chrysophyte assemblages from dated lake sediment cores indicate that all the lakes have been impacted by anthropogenic acidification, although the timing and the magnitude of acidification were different amongst the lakes. For example, Whirligig Lake was likely the most naturally acidic lake in the past, but it had further acidified since about 1960. This lake was limed in 1989 and then again in 1993. In Whitepine Lake, acidification started 1940; however, in the most recent sediments (1992), some recovery in lakewater acidity has occurred. In Little Whitepine Lake (a reference lake), acidification started earlier (1920) and the lakewater pH continued to decline until about 1990. This lake was limed in 1989. The chrysophyte paleoindicators suggest a recent recovery in this lake. The successful re-introduction of aurora trout in Whirligig and Whitepine lakes is undoubtedly related to the improved water quality through liming but, based on our paleolimnological indicators, the lakes' limnological characteristics (e.g. pH and metal concentrations) are still different from those present before atmospheric deposition of strong acids from the Sudbury smelters.     

Immobilized cyanobacteria as a biofertilizer for rice crops; Intl. Conference on Applied Algology, Knysna, South Africa, April 1996.

N₂-fixing cyanobacteria (Anabaena azollae, symbiont strains) were immobilized in polyurethane foam and ammonia production by the cyanobacteria was investigated in the laboratory and rice field. The cyanobacterial symbiont, A. azollae - MPK-SK-AM-24 showed the highest growth rate and biomass production amongst the 5 isolates examined while A. azollae-AS-DS showed the highest nitrogenase activity followed by A. variabilis - SA₀ (wild type, non-symbiotic). Treatment of the foam-immobilized cyanobacteria with the systemic fungicide Bavistin stimulated nitrogenase activity while inhibiting glutamine synthetase (GS) activity. Free-living A. azollae-MPK-SK-AF-38, A. azollae - MPK-SK-AM-24 and A. azollae-MPK-SK-AM-27 excreted the highest amounts of ammonia into the growth medium; under foam - immobilized conditions the ammonia production increased further. Treatment of the foam - immobilized cyanobacteria with the fungicides Bavistin and Vitavax resulted in ammonia production at significantly higher rates. Rice seedlings (var. ADT 36) grown in the laboratory in conjunction with foam - immobilized A. azollae showed increased growth. A field experiment with paddy rice and foam - immobilized A. azollae strains indicated that the cyanobacteria excreted significant amounts of ammonia into the flood water in the rice fields resulting in increased chlorophyll content of the plants and increased the rice grain and straw yields. A combination of fertilizer nitrogen and inoculation with foam - immobilized cyanobacteria also significantly increased the rice grain and straw yield. Additionally, both A. azollae and A. variabilis were immobilized in sugarcane waste (bagasse), added to rice paddy and resulted in increased rice grain yield. This revised version was published online in September 2006 with corrections to the Cover Date.     

Enhanced Immune Responses to HIV-1 Envelope Elicited by a Vaccine Regimen Consisting of Priming with Newcastle Disease Virus Expressing HIV gp160 and Boosting with gp120 and SOSIP gp140 Proteins

Newcastle disease virus (NDV) expressing HIV-1 BaL gp160 was evaluated either alone or with monomeric BaL gp120 and BaL SOSIP gp140 protein in a prime-boost combination in guinea pigs to enhance envelope (Env)-specific humoral and mucosal immune responses. We showed that a regimen consisting of an NDV prime followed by a protein boost elicited stronger serum and mucosal Th-1-biased IgG responses and neutralizing antibody responses than NDV-only immunizations. Additionally, these responses were higher after the gp120 than after the SOSIP gp140 protein boost.     

Gastric dilatation and intestinal obstruction mimicking acute coronary syndrome with dynamic electrocardiographic changes

Background

Hyperuricemia may be associated with an increased risk of coronary heart disease (CHD) mortality; however, the results from prospective studies are conflicting. The objective of this study was to assess the association between hyperuricemia and risk of CHD mortality by performing a meta-analysis.

Methods

Pubmed and Embase were searched for relevant prospective cohort studies published until July 2015. Studies were included only if they reported data on CHD mortality related to hyperuricemia in a general population. The pooled adjusted relative risk (RR) was calculated using a random-effects model.

Results

A total of 14 studies involving 341 389 adults were identified. Hyperuricemia was associated with an increased risk of CHD mortality (RR: 1.14; 95 % CI: 1.06–1.23) and all-cause mortality (RR: 1.20; 95 % CI: 1.13–1.28). For each increase of 1 mg/dl of serum uric acid (SUA), the overall risks of CHD and all-cause mortality increased by 20 and 9 %, respectively. According to the gender subgroup analyses, hyperuricemia increased the risk of CHD mortality in women (RR: 1.47; 95 % CI: 1.21–1.73) compared to men (RR: 1.10; 95 % CI: 1.00–1.19). The risk of all-cause mortality was greater in women.

Conclusions

Hyperuricemia may modestly increase the risk of CHD and all-cause mortality. Future research is needed to determine whether urate–lowering therapy has beneficial effects for reducing CHD mortality.