In vitro evaluation of antioxidant and radioprotective properties of a novel extremophile from mud volcano: implications for management of radiation emergencies

A thermophilic bacterium, designated as RH 127, was isolated from mud volcano (Baratang Islands) of Andaman region, India (12°07'N 92°47'E/12.117°N 92.783°E) for the first time. Biochemical tests and 16S rRNA gene sequencing indicate that it belongs to the genus Geobacillus. The strain showed 98% confirmed 16S rRNA gene sequence homology with Geobacillus toebii. The bacteria was extracted in various solvent systems and three different fractions prepared. In the present study, antioxidant and radioprotective activity of extracts (INM-7860, INM-7861, and INM-7862) of bacterium G. toebii (strain RH 127) were evaluated. The fractions were evaluated for their introspective comparison of the relative antioxidant efficiency. The antioxidative activities, DPPH radical scavenging effects, hydroxyl radical scavenging effects, membrane protection, antihemolytic activity, and linoleic acid degradation efficacies were assayed. INM-7861 and INM-7862 activated NF-κB expression, as evidenced by reporter assay studies, and thereby contributed to overall radioprotective effect. INM-7862 exhibited best results. This study explicitly shows that the extracts of G. toebii have immense potential as a radiation countermeasure agent.     

Elevated levels of NO are localized to distal airways in asthma

The contribution of nitric oxide (NO) to the pathophysiology of asthma remains incompletely defined despite its established pro- and anti-inflammatory effects. Induction of the inducible nitric oxide synthase (iNOS), arginase, and superoxide pathways is correlated with increased airway hyperresponsiveness in asthmatic subjects. To determine the contributions of these pathways in proximal and distal airways, we compared bronchial wash (BW) to traditional bronchoalveolar lavage (BAL) for measurements of reactive nitrogen/oxygen species, arginase activation, and cytokine/chemokine levels in asthmatic and normal subjects. Levels of NO were preferentially elevated in the BAL, demonstrating higher level NOS activation in the distal airway compartment of asthmatic subjects. In contrast, DHE(+) cells, which have the potential to generate reactive oxygen species, were increased in both proximal and distal airway compartments of asthmatics compared to controls. Different patterns of cytokines and chemokines were observed, with a predominance of epithelial cell-associated mediators in the BW compared to macrophage/monocyte-derived mediators in the BAL of asthmatic subjects. Our study demonstrates differential production of reactive species and soluble mediators within the distal airways compared to the proximal airways in asthma. These results indicate that cellular mechanisms are activated in the distal airways of asthmatics and must be considered in the development of therapeutic strategies for this chronic inflammatory disorder.     

Biodegradation of paddy straw obtained from different geographic locations by means of <Emphasis Type="Italic">Phlebia</Emphasis> spp. for animal feed

Various cereal straws are used as feed by supplementing the green forage or other feed stuffs. An experiment was designed to see the effect of different geographic locations and climatological conditions on biochemical constituents, fungal degradation and in vitro digestibility of paddy straw. Paddy straw (PS) obtained from three different geographic locations of India was subjected to solid state fermentation using four white rot fungi i.e. Phlebia brevispora, P. fascicularia, P. floridensis and P. radiata. Changes in the biochemical constituents like water soluble content, hemicellulose, cellulose, lignin, total organic matter, and in vitro digestibility of paddy straw was analyzed over a period of 60 days along with lignocellulolytic enzymes i.e. laccase, xylanase and carboxymethyl cellulase. All the fungi degraded the straw samples and enhanced the in vitro digestibility. The paddy straw, obtained from north western zone (NWZ) suffered a maximum loss (228 g/kg) of lignin by P. radiata, while a maximum enhancement of in vitro digestibility from 185 to 256 g/kg was achieved by P. brevispora, which also caused minimum loss in total organic matter (98 g/kg). In PS obtained from central eastern zone (CEZ) and north eastern zone (NEZ), a maximum amount of lignin (210 and 195 g/kg, respectively) was degraded by P. floridensis and resulted into a respective enhancement of in vitro digestibility from 172 to 246 g/kg and 188 to 264 g/kg. The study demonstrates that geographic locations not only affect the biochemical constituents of paddy straw but the fungal degradation of fibers, their in vitro digestibility and lignocellulolytic enzyme activity of the fungus may also vary.     

Synthesis and anti-inflammatory activity of novel biscoumarin-chalcone hybrids

A series of synthesized novel biscoumarin-chalcone hybrids were evaluated for their anti-inflammatory and antioxidant activity. The tested compounds significantly inhibit the carrageenin induced paw oedema in albino rats and also exhibit important scavenging activities. These compounds thus constitute an interesting template for the design of new therapeutic tools against inflammation.     

Synthesis and antihyperglycemic activity of phenolic C-glycosides

Various phenolic C-glycosides were evaluated for their in vitro and in vivo antihyperglycemic activity employing glucose uptake by rat muscle cell lines (L-6) and low dosed-streptozotocin-induced diabetic rats, respectively. Some of phenolic C-glycosides were isolated from Pterocarpus marsupium and Ulmus wallichiana and other were synthesized by unprotected sugar and phloroacetophenone using Sc(OTf)₃ in aqueous ethanol. Eight among tested compounds showed significant lowering of blood glucose level on low dosed-streptozotocin-induced diabetic rats. The compound 24 lowered the blood glucose levels by 34.9% and 33.6% during 0-5 h and 0-24 h, respectively, at the dose of 25 mg/kg body weight which is comparable to standard antidiabetic drug metformin.     

Solid state degradation of paddy straw by Phlebia floridensis in the presence of different supplements for improving its nutritive status

Effect of different supplements on the degradation of paddy (rice) straw by Phlebia floridensis was studied and the conditions for best ligninolysis, lower loss in total organic matter (TOM) and enhancement in in vitro digestibility (IVD) were established. Effect of different supplements on lignocellulolytic enzymes production, degradation of cell wall fibres of paddy straw and their resultant effect on its nutritional quality was studied. Ammonium chloride, soya bean meal and moisture content were selected for response surface study on the basis of their important role in degradation. Finally, the process was successfully scaled up from 5 g to 200 g under optimized sold state conditions and the straw quality was upgraded in terms of increased IVD (40%) with a moderate loss (6%) in TOM during 20 days of incubation. Protein content, amino acid, total phenolics and antioxidant properties of the paddy straw improved with its fermentation.     

Daidzein prevents the increase in CD4+CD28null T cells and B lymphopoesis in ovariectomized mice: a key mechanism for anti-osteoclastogenic effect

Estrogen deficiency leads to an upregulation of TNF-α producing T cells and B-lymphopoesis which augments osteoclastogenesis. Estrogen deficiency also increases the population of premature senescent CD4⁺CD28null T cells which secrete a higher amount of TNF-α thus leading to enhanced osteoclastogenesis. Isoflavonoids like daidzein and genistein are found mostly in soybeans, legumes, and peas. These share structural similarity with 17β-stradiol (E2) and have osteoprotective role. This study explores the effect of daidzein (Daid) on the proliferation of TNF-α producing T cells, premature senescent T cells and B cell lymphopoesis under estrogen deficient conditions. For this study adult Balb/c mice were treated with Daid at 10 mg/kg body weight dose by oral gavage daily post ovariectomy (Ovx). After six weeks animals were autopsied and bone marrow and spleen cells were collected for FACS analysis. Blood serum was collected for ELISA. It was observed that Ovx mice treated with Daid for six weeks show reduction in Ovx induced expansion of CD4⁺ T cells in bone marrow and spleen when analysed by flow cytometry. Estrogen deficiency led to increased prevalence of TNF-α secreting CD4⁺CD28null T cells, however, treatment with Daid increased the percentage of CD4⁺CD28⁺ T cells. Co-culture of CD4⁺CD28null T cells and bone marrow resulted in enhanced osteoclastogenesis as evident by increased tartarate resistant acid phosphatase (TRAP) expression, an osteoclast marker. However, treatment with Daid resulted in reduced osteoclastogenesis in CD4⁺CD28null T cells and bone marrow cell co-culture. Daid also regulated B lymphopoesis and decreased mRNA levels of RANKL in B220⁺ cells. Taken together, we propose that one of the mechanisms by which Daid prevents bone loss is by reversing the detrimental immune changes as a result of estrogen deficiency.     

Evaluation of 5-[1-(2-Halo(or nitro)ethoxy-2-iodoethyl)]-2′-deoxyuridines as Inhibitors of Herpes Simplex Virus

A series of 5-[1-(2-haloethyl(or nitro)ethoxy-2-iodoethyl)]-2′-deoxyuridines (3 - 7) and related uracil analogs (9 - 10) were prepared using 5-vinyl-2′-deoxyuridine (2) and 5-vinyl uracil (8) as starting materials. The regiospecific reaction of 2 and 8 with iodine monochloride and an alcohol provided the target compounds 3 - 10. These analogs were evaluated in vitro for inhibitory activity against thymidine-kinase (TK) positive and negative strains of herpes simplex virus type-1. The compounds 3 - 10 were either weak or non-inhibitory to HSV-1 replication. All compounds investigated exhibited low host cell cytotoxicity.     

Mitochondrial DNA variations in Madras motor neuron disease

Although the Madras motor neuron disease (MMND) was found three decades ago, its genetic basis has not been elucidated, so far. The symptom at onset was impaired hearing, upper limb weakness and atrophy. Since some clinical features of MMND overlap with mitochondrial disorders, we analyzed the complete mitochondrial genome of 45 MMND patients and found 396 variations, including 13 disease-associated, 2 mt-tRNA and 33 non-synonymous (16 MT-ND, 10 MT-CO, 3 MT-CYB and 4 MT-ATPase). A rare variant (m.8302A>G) in mt-tRNA^Leu was found in three patients. We predict that these variation(s) may influence the disease pathogenesis along with some unknown factor(s).