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Abstract A novel antibacterial immunostimulant using Platinum nanoparticles (PtNPs) and lectin from Metapenaeus dobsoni (Md-Lec) was developed. The Md-Lec and PtNPs (Pt-lec) hybrid formed through non-covalent interaction exhibits antimicrobial activity against fish specific pathogens by affecting membrane integrity and producing excess reactive oxygen species. The therapeutic efficacy of Pt-lec was demonstrated through rescuing Aeromonas hydrophila infected Nile Tilapia. Pt-lec prevents the infection spreading and reduces the bacterial bioburden in less than 12 h, and as a result of this the fish were restored to normalcy. To assess immunostimulation, we studied the expression of three different immune related genes, namely LEC, Myd88 and COX-2 in the gills, liver, spleen and kidney of fish under various experimental conditions. Our results showed that Pt-lec treatment appeared to be better when compared to lectin alone in enhancing the expression of Myd88 and COX-2, but LEC was not as expected. These results suggest that Pt-lec has the ability to protect Nile Tilapia against bacterial infection by restricting bacterial bioburden through their direct effects on the bacterial membrane and indirectly through their effects on host immune-related gene expression. This hybrid could have potential “green” application in fish farming in rescuing infected animals when compared to widely and unregulated antibiotics.

Abstract Infectious bacteria in biofilm mode are involved in many persistent infections. Owing to its importance in clinical settings, many in vitro and in vivo studies are being conducted to study the structural and functional properties of biofilms, their drug resistant mechanism and the s urvival mechanism of planktonic and biofilm cells. In this regard, there is not sufficient information on the interaction between Klebsiella biofilm and macrophages. In this study, we have attempted to unravel the interaction between Klebsiella biofilm and macrophages in terms of phagocytic response and cytokine expression. In vitro phagocytosis assays were performed for heat inactivated and live biofilms of K. pneumoniae, together with the expression analysis of TLR2, iNOS, inflammatory cytokines such as IL-β1, IFN-γ, IL-6, IL-12, IL-4, TNF-α and anti-inflammatory cytokine, IL-10. A phagocytic rate of an average of 15% was observed against both heat inactivated and live biofilms when LPS + IFN-γ activated macrophages were used. This was significantly higher than non-activated macrophages when tested against heat inactivated and live biofilms (average 8%). Heat-inactivated and live biofilms induced similar phagocytic responses and up-regulation of pro-inflammatory genes in macrophages, indirectly conveying that macrophage responses are to some extent dependent on the biofilm matrix.

Microplastic (MPs) contamination has emerged as a serious worldwide issue. Human activity, commercial enterprises, and fishing are concentrated around the seashore, causing high levels of MPs contamination in coastal and marine organisms. When it comes to their vulnerability to MPs ingestion, sharks are least studied organism. The objective of this study is to investigate MPs accumulation in sharks collected from the Southeast Indian coastal zone (Bay of Bengal). We present evidence of MPs ingestion in demersal sharks caught by the trawlers during trawling operations in marine waters beyond a depth of 80 m in the Southeast India coast. Shark samples were also checked for any gender or size differences in contaminant loading. Gill and gut (digestive tract) were examined in 40 sharks and 82.5% of samples contained at least one MP particle. The average number of MP particles was found to be 4.67 items per individual shark; the gastrointestinal tract showed more MPs than the gills. The majority of the MPs were blue and pale white followed by black and transparent particles with diameters ranging from 0.5 to 2 mm. The fibre fragments were prevalent in the intestines of the shark. Fourier Transform Infrared (FT-IR) spectroscopy revealed that the bulk of polymers were polypropylene (PP), polyacrylamides (PA), and polyethylene (PE). MPs contamination poses an unknown level of harm to shark species. The present study revealed the first scientific data of MPs and associated fibre ingestion in shark species in their habitat in the Bay of Bengal.

Abstract Colistin resistance in Enterobacteriaceae especially Klebsiella pneumoniae and Escherichia coli is driving the evolution of pan drug resistant strains. Screening a library of 13 plant nutraceuticals led to the identification of acetyl shikonin and ursolic acid, which exhibited synergy with colistin against extremely drug resistant (XDR) clinical strains of E. coli (U3790) and K. pneumoniae (BC936). Ursolic acid caused a significant colistin MIC reversal of 16-fold in U3790 and 4-fold in BC936 strains. Ursolic acid also potentiated the bactericidal effect of colistin against both U3790 and BC936 by causing ~ 4 to 4.5 log fold decline in CFU of both clinical isolates in a time kill assay. At 2× minimum effective concentration, ursolic acid was non-toxic to zebrafish as evidenced by brain and liver enzyme profiles and by histopathology studies. In combination with colistin, ursolic acid reduced bacterial bioburden of U3790/BC936 by 1–1.58 log fold from the infected muscle tissue of zebrafish. Mechanistic explorations via studies on real time efflux, membrane potential and intracellular accumulation of dansyl chloride tagged colistin revealed that colistin efflux is inhibited by ursolic acid. In addition, ursolic acid also enhanced outer membrane permeability which probably facilitates colistin’s attack on outer and inner membranes. Our study shows that ursolic acid synergizes with colistin by inhibiting colistin efflux in Enterobacteriaceae that helps to curtail colistin resistant Enterobacteriaceae.

The emergence and spread of pathogens harboring extended spectrum beta-lactamase (ESBL) like carbapenem resistant Gram negative bacteria are the major emerging threat to public health. Of particular concern Klebsiella pneumoniae carbapenamase- producing strains have been recorded worldwide. Catheter associated urinary tract infections (CAUTI) caused by K. pneumoniae are significantly associated with morbidity and mortality. Hence the present work was aimed to develop a strategy for addressing these issues through an innovative approach of antibiofilm and immunomodulation. These two independent activities were analyzed in a Streptomyces derived ASK2 bioactive compound. While analysing the effect of sub-minimum inhibitory concentrations (sub-MICs), 0.5x of Minimum Inhibitory Concentration (MIC) was found to be more effective in preventing biofilm formation on coverslip and silicone catheter. The minimum biofilm eradication concentration (MBEC) was found to be 15-fold higher MIC with eradication of 75% of 3 day old biofilm. Apart from its antibiofilm potential, ASK2 also acts as an opsonin and enhances phagocytic response of macrophages against multidrug resistant K. pneumoniae. In addition, ASK2 resulted in elevated levels of nitric oxide generation by the macrophages and has a stimulating effect on IL-12, IFN-γ, and TNF-α proinflammatory cytokines. The opsonic role of ASK2 and its potential in modulating proinflammatory cytokines secreted by macrophages implies the importance of ASK2 in modulating cellular immune response of macrophages against MDR K. pneumoniae. The present study proposes ASK2 as a promising candidate for treating MDR K. pneumoniae infections with its dual properties of antibiofilm and immunomodulatory activities.

Cataracts, glaucoma, and age-related macular degeneration are known as major ocular problems which cause blindness among the elderly population worldwide. Oxidative stress plays an important role in both the initiation and progression of ocular problems and with respect to this; dietary antioxidants can serve as a therapeutic strategy for the improvement of ocular health. Zeaxanthin is known as one of the most important and common xanthophyll carotenoids, possessing multiple therapeutic effects such as strong antioxidant and pro-oxidant behaviour as well as anti-inflammatory effects. A growing body of literature shows that zeaxanthin mitigates ocular problems and suppresses oxidative stress in the retinal tissues. This paper aims to critically review the available literature regarding the beneficial effects of zeaxanthin on ocular problems with emphasis on its chemistry, bioavailability, and sources. [ABSTRACT FROM AUTHOR]

The pathogenesis of glycerol-induced myoglobinuric acute renal failure involves ischemia, vascular congestion and reactive oxygen metabolites. In this study, we have investigated for the first time, the role of ferulic acid in attenuating glycerol-induced nephrotoxicity. Male Wistar rats were injected intramuscularly with 8 mL/kg body weight of 50% glycerol, glycerol + ferulic acid at the dose of 5, 10, 15, 20 and 25 mg/kg body weight. After 24 h, the rats were sacrificed and the kidneys were removed for histological and immunohistochemical studies. Furthermore, determinations of lipid peroxidation (LPO) as well as antioxidant enzymes were also analyzed; blood, urine samples were collected in order to quantify renal function and nitric oxide generation, respectively. Glycerol-induced rats showed a significant increase in the level of urinary markers assessed in serum as well as kidney and these were reversed upon ferulic acid treatment. A significant increase in urine nitric oxide, serum as well as kidney LPO, decrease in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione were observed in glycerol-induced rats. Immunohistochemical study in glycerol-induced rats demonstrated an increase in the level of nuclear factor-kappaB (NF-κB). All these effects induced by glycerol were reduced upon treatment with ferulic acid in a dose-dependent manner. To conclude, ferulic acid enhances antioxidants and decreases NF-κB, thereby protecting the cells against stress induced by glycerol. [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate the effect of curcumin in protecting against selenium-induced toxicity in liver and kidney of Wistar rats. Light microscopy evaluation of selenium alone administered rats showed liver to be infiltrated with mononuclear cells, vacuolation, necrosis, and pronounced degeneration. Control liver sections showed a regular morphology of parenchymal cells with intact hepatocytes and sinusoids. Kidney from selenium alone administered rats showed vacuolar degeneration changes in the epithelial cells, cellular proliferation with fibrosis, thickening of capillary walls, and glomerular tuft atrophy. Such changes were also observed in rats administered with selenium and curcumin simultaneously and rats administered first with selenium and then curcumin 24 h later. Interestingly, such degenerative changes observed in liver and kidney induced by selenium were not seen in rats that were administered with curcumin first and selenium 24 h later. This clearly suggests the protective nature of curcumin against selenium toxicity. To understand the probable mechanism of action of curcumin, we analyzed inducible nitric oxide synthase (iNOS) expression by immunohistochemistry, and the results showed an increased iNOS expression in selenium-alone induced liver and kidney. Such high iNOS levels were inhibited in liver and kidney of rats pretreated with curcumin and then with selenium 24 h later. Based on the histological results, it can be concluded that curcumin functions as a protective agent against selenium-induced toxicity in liver as well as kidney, and this action is probably by the regulatory role of curcumin on iNOS expression. Microsc. Res. Tech., 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The aim of the present study is to evaluate the effect of hot water extract of black tea in regenerating β cells in streptozotocin-induced diabetic mice. Light microscopic examination of pancreatic sections of streptozotocin-induced diabetic mice showed the acinar cells to be small, shrunken, and with deteriorated β cells. The dose of streptozotocin not only altered the function of β cells but also damaged the acinar region. The changes in acinar cells were coarsening of endoplasmic reticulation suggesting alteration in their secretory function. The control pancreatic tissue showed well-defined granulated islets and dark β cells when stained with chrome hematoxylin and phloxine. Interestingly, pancreatic sections of diabetic mice fed with black-tea extract showed regeneration of β cells and acinar region appeared normal with increased numbers of β cells. To understand the probable mechanism of action of black-tea extract, we analyzed inducible nitric oxide synthase (iNOS) expression by immunohistochemistry and the results showed an increased iNOS levels in streptozotocin-induced diabetic pancreas, and such high iNOS levels were inhibited in black-tea extract treated mice. According to histological results obtained, it can be concluded that the black-tea extract helps in regeneration of damaged pancreas and protects pancreatic β cells by its antioxidant action against nitrosative stress in streptozotocin-induced diabetes. Microsc. Res. Tech., 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Curcumin is the yellow-colored bioactive constituent of the perennial plant, Curcuma longa L., which possesses a wide range of physiological and pharmacological properties such as antioxidant, anti-inflammatory, anticancer, neuroprotective and anti-diabetic activities. Anti-diabetic activity of curcumin may be due to its potent ability to suppress oxidative stress and inflammation. Moreover, it shows a beneficial role on the diabetesinduced endothelial dysfunction and induces a down-regulation of nuclear factor-kappa B. Curcumin possesses a protective role against advanced glycation as well as collagen crosslinking and through this way, mitigates advanced glycation end products-induced complications of diabetes. Curcumin also reduces blood glucose, and the levels of glycosylated hemoglobin in diabetic rat through the regulation of polyol pathway. It also suppresses increased bone resorption through the inhibition of osteoclastogenesis and expression of the AP-1 transcription factors, c-fos and c-jun, in diabetic animals. Overall, scientific literature shows that curcumin possesses anti-diabetic effects and mitigates diabetes complications. Here we report a systematical discussion on the beneficial role of curcumin on diabetes and its complications with emphasis on its molecular mechanisms of actions.

The aim of this study is to investigate the mechanism of an action of compound isolated from Vitex negundo in streptozotocin-induced diabetic mice. Light microscopic examination of liver, kidney and pancreatic sections of streptozotocin-induced diabetic mice showed changes like coarsening of acinar cells of endoplasmic reticulum, destruction of β-cells, and alteration in their secretory function were observed in the pancreas. Changes like dilation of vein, unusual concentric arrangement of hepatocytes, and liver fibrosis were observed in the liver. Thickening of tubules and expansion of glomerulus were observed in kidneys. All these altered parameters were reversed close to normal condition upon treatment using idopyranose. The results show the antidiabetic potential of idopyranose. Interestingly, liver, kidney, and pancreatic sections of diabetic mice fed with the isolated 1, 2 di-substituted idopyranose showed regeneration of hepatocytes, nephrocytes, as well as β-cells and acinar region appeared normal with increased numbers of β-cells. To understand the probable mechanism of action of 1, 2 di-substituted idopyranose, we analyzed proinflammatory inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) expression by immunohistochemistry and the results showed an increased iNOS and NF-κB levels in streptozotocin-induced diabetic liver, kidney and pancreas. Such high iNOS and NF-κB levels were inhibited in 1, 2 di-substituted idopyranose treated mice. The results suggest that 1, 2 di-substituted idopyranose helps in the protection of hepatocytes, nephrocytes and pancreatic β-cells probably by its action against NF-κB and iNOS mediated inflammation in streptozotocin-induced diabetes., (Copyright © 2010 Wiley-Liss, Inc.)

The hemocytes from the giant freshwater prawn Macrobrachium rosenbergii were examined for their ability to generate superoxide anion (O(2) (-)) in vitro upon exposure to various components derived from microbial cell wall components. Among the test molecules, laminarin (a polymer of beta-1, 3 glucans), mannan and LPS from five different bacterial species produced a differential response in terms of stimulated O(2) (-) production in prawn hemocytes, suggesting the ability of the hemocytes to differentiate non-self. This response was almost completely inhibited by superoxide dismutase (SOD) suggesting SOD-inhibitable O(2) (-) generation by prawn hemocytes. Phorbol 12-myristate 13-acetate (PMA) and Ca ionophore led to enhanced O(2) (-) generation by the hemocytes and this suggests the possible role of protein kinase C and Ca(2+) ions in such generation. Cytochemical analysis using nitroblue tetrazolium (NBT)-staining revealed the importance of granular hemocytes in O(2) (-) generation in these prawns. Inhibition of O(2) (-) generation by inhibitors of NADPH-oxidase and phenoloxidase pathways clearly reveal the involvement of two different pathways in non-self stimulated O(2) (-) generation by the prawn hemocytes. These findings demonstrate the importance of O(2) (-) generation and role of possible pathways in hemocyte mediated cellular immune response of a crustacean.