Narayan C. Mandal

Chronic inflammation and cancer: potential chemoprevention through nuclear factor kappa B and p53 mutual antagonism

Activation of nuclear factor-kappa B (NF- κ B) as a mechanism of host defense against infection and stress is the central mediator of inflammatory responses. A normal (acute) inflammatory response is activated on urgent basis and is auto-regulated. Chronic inflammation that results due to failure in the regulatory mechanism, however, is largely considered as a critical determinant in the initiation and progression of various forms of cancer. Mechanistically, NF- κ B favors this process by inducing various genes responsible for cell survival, proliferation, migration, invasion while at the same time antagonizing growth regulators including tumor suppressor p53. It has been shown by various independent investigations that a down regulation of NF- κ B activity directly, or indirectly through the activation of the p53 pathway reduces tumor growth substantially. Therefore, there is a huge effort driven by many laboratories to understand the NF- κ B signaling pathways to intervene the function of this crucial player in inflammation and tumorigenesis in order to find an effective inhibitor directly, or through the p53 tumor suppressor. We discuss here on the role of NF- κ B in chronic inflammation and cancer, highlighting mutual antagonism between NF- κ B and p53 pathways in the process. We also discuss prospective pharmacological modulators of these two pathways, including those that were already tested to affect this mutual antagonism.

Sunlight-induced rapid and efficient biogenic synthesis of silver nanoparticles using aqueous leaf extract of Ocimum sanctum Linn. with enhanced antibacterial activity

Background Nanotechnology is now regarded as a distinct field of research in modern science and technology with multifaceted areas including biomedical applications. Among the various approaches currently available for the generation of metallic nanoparticles, biogenic synthesis is of increasing demand for the purpose of green nanotechnology. Among various natural sources, plant materials are the most readily available template-directing matrix offering cost-effectiveness, eco-friendliness, and easy handling. Moreover, the inherent pharmacological potentials of these medicinal plant extracts offer added biomedical implementations of the synthesized metal nanoparticles. Results A robust practical method for eco-friendly synthesis of silver nanoparticles using aqueous leaf extract of Ocimum sanctum (Tulsi) as both reducing and capping agent, under the influence of direct sunlight has been developed without applying any other chemical additives. The nanoparticles were characterized with the help of UV-visible spectrophotometer and transmission electron microscopy (TEM). The prepared silver nanoparticles exhibited considerable antibacterial activity. The effects were more pronounced on non-endospore-forming Gram-positive bacteria viz., Staphylococcus aureus, Staphylococcus epidermidis, and Listeria monocytogenes than endospore-forming species Bacillus subtilis. The nanoparticles also showed prominent activity on Gram-negative human pathogenic Salmonella typhimurium, Escherichia coli, Pseudomonas aeruginosa, and plant pathogenic Pantoea ananatis. A bactericidal mode of action was observed for both Gram-positive and Gram-negative bacteria by the nanoparticles. Conclusions We have developed a very simple, efficient, and practical method for the synthesis of silver nanoparticles using aqueous leaf extract of O. sanctum under the influence of direct sunlight. The biosynthesis of silver nanoparticles making use of such a traditionally important medicinal plant without applying any other chemical additives, thus offers a cost-effective and environmentally benign route for their large-scale commercial production. The nanoparticles dispersed in the mother solution showed promising antibacterial efficacy.Graphical Abstract Sunlight-induced rapid and efficient biogenic synthesis of silver nanoparticles using aqueous leaf extract of Ocimum sanctum Linn. with enhanced antibacterial activity. Electronic supplementary material The online version of this article (doi:10.1186/s13588-014-0018-6) contains supplementary material, which is available to authorized users.

Production and partial characterisation of an inducer-dependent novel antifungal compound(s) by Pediococcus acidilactici LAB 5

BACKGROUND Pediococcus acidilactici LAB 5 produces an antifungal compound under in vitro conditions in an inducer-dependent manner. The main objective of the present study was to partially characterise this antifungal compound by UV-visible, IR, (1)H NMR, (13)C NMR and GC/MS analyses and also to assess its potentiality against a number of food spoilage, plant-pathogenic and human-pathogenic fungal species. RESULTS The strain produced a broad-spectrum antifungal compound(s) that was induced by certain constituent factors of MRS and malt extract media. The production was higher in solid culture than in broth culture. The product was found to be a mixture of lactic acid and a compound of molecular mass 83. The minimum inhibitory concentrations (MIC90, 1.32-2.86 g L(-1)) of the active extract were much lower than those of sodium benzoate and calcium propionate. Scanning electron micrographs proved its drastic action on the development of conidial structures. CONCLUSION The chemical analysis indicated a novel compound with fungicidal activity. This compound could be used in fermented foods and feeds to extend their shelf life and also in agricultural crop plants against certain fungal pathogens.

Evaluation of the Antimicrobial Potential of Two Flavonoids Isolated from Limnophila Plants

The antimicrobial potential of two bioflavonoids, i.e., 5,7‐dihydroxy‐4′,6,8‐trimethoxyflavone (1) and 5,6‐dihydroxy‐4′,7,8‐trimethoxyflavone (2), isolated from Limnophila heterophylla Benth. and L. indica (Linn.) Druce (Scrophulariaceae), respectively, were evaluated against the microbial strains Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, Alternaria solani, and Candida albicans. Compounds 1 and 2 exhibited moderate but broad antimicrobial activities against both Gram‐positive and Gram‐negative bacteria and also against the fungal pathogens. Moreover, the mechanism of action of 1 and 2 on the cellular functions or structures of some of the microorganisms was studied. Compound 1 showed a bactericidal effect against E. coli and S. aureus (MICs of 200 and 250 μg/ml, resp.), while compound 2 was found to effectively kill B. subtilis by cell lysis. The growth of A. solani and C. albicans was inhibited by compounds 1 and 2, respectively. The effects of the flavonoids on the cellular structures and the carbohydrate metabolic pathways were studied by scanning electron microscopy (SEM) of the treated cells and by assessing the specific activity of key enzymes of the pathways, respectively. At sublethal doses, they enhanced the activity of gluconeogenic fructose bisphosphatase, but decreased the activity of phosphofructokinase and isocitrate dehydrogenase, the key enzymes of the EmbdenMeyerhofParnas pathway and the tricarboxylic acid cycle, respectively.

Role of phosphate solubilizing Burkholderia spp. for successful colonization and growth promotion of Lycopodium cernuum L. (Lycopodiaceae) in lateritic belt of Birbhum district of West Bengal, India

Profuse growth of Lycpodium cernuum L. was found in phosphate deficient red lateritic soil of West Bengal, India. Interaction of vesicular-arbuscular mycorrhiza (VAM) with Lycopodium rhizoids were described earlier but association of PGPR with their rhizoids were not studied. Three potent phosphate solubilizing bacterial strains (P4, P9 and P10) associated with L. cernuum rhizoids were isolated and identified by 16S rDNA homologies on Ez-Taxon database as Burkholderia tropica, Burkholderia unamae and Burkholderia cepacia respectively. Day wise kinetics of phosphate solubilization against Ca3(PO4)2 suggested P4 (580.56±13.38 μg ml(-1)) as maximum mineral phosphate solubilizer followed by P9 (517.12±17.15 μg ml(-1)) and P10 (485.18±14.23 μg ml(-1)) at 28 °C. Release of bound phosphates by isolated strains from ferric phosphate (FePO4), aluminum phosphate (AlPO4) and four different complex rock phosphates indicated their very good phosphate solubilizng efficacy. Nitrogen independent solubilizition also supports their nitrogen fixing capabilities. Inhibition of P solubilization by calcium salts and induction by EDTA suggested pH dependent chelation of metal cations by all of the isolates. Rhizoidal colonization potentials of Burkholderia spp. were confirmed by in planta experiment and also using scanning electron microscope (SEM). Increases of total phosphate content in Lycopodium plants upon soil treatment with these isolates were also recorded. In addition siderophore production on CAS agar medium, tryptophan dependent IAA production and antifungal activities against pathogenic fungi by rhizospheric isolates deep-rooted that they have definite role in nutrient mobilization for successful colonization of L. cernuum in nutrient deficient lateritic soil.

The Study of Cyanobacterial Flora from Geothermal Springs of Bakreswar, West Bengal, India

Geothermal springs in India, formed as a result of volcanic or tectonic activities, are characterized by high temperature and relatively abundant reduced compounds. These thermal springs are inhabited by characteristic thermophilic organisms including cyanobacteria. Cyanobacteria are among the few organisms that can occupy high temperature aquatic environments including hot springs. In alkaline and neutral hot springs and streams flowing from them cyanobacteria can form thick colourful mats that exhibit banding patterns. The present investigation involves study of mat forming cyanobacterial flora from hot springs located in Bakreswar, West Bengal, India. The important species found are Synechococcus bigranulatus, S. lividus, Gloeocapsa gelatinosa, G. muralis, Phormidium laminosum, P. frigidum, Oscillatoria princes, O. fragilis, Lyngbya lutea, Pseudanabaena sp., Calothrix thermalis, and Fischerella thermalis. Their distribution pattern in relation to physico-chemical parameters of spring water has also been studied. Three cyanobacterial strains of the above mentioned list were grown in culture and their pigment content and nitrogen fixing capacity were also studied. Nitrogen fixing capacities of Calothrix thermalis, Nostoc sp. (isolated in culture) and Fischerella thermalis are 5.14, 0.29, and 2.60 n mole C2H4/µg of Chl-a/hr respectively. Carotenoid : Chlorophyll-a ratio of four mat samples collected from Kharkunda, Suryakunda, Dudhkunda and bathing pool are 2.45, 1.60, 1.48, and 1.34, respectively. Higher value of Carotenoid : Chlorophyll-a ratio coincided with higher temperature.

A new pentacyclic triterpene with potent antibacterial activity from Limnophila indica Linn. (Druce)

A new pentacyclic triterpenoid constituent, characterized as 3-oxo-olean-12(13),18(19)-dien-29α-carboxylic acid (1) on the basis of detailed spectral studies, was isolated from the aerial parts and roots of Limnophila indica (Scrophulariaceae). Compound 1 exhibited considerable antibacterial activity against three Gram-positive bacteria viz. Bacillus subtilis, Staphylococcus aureus and Listeria monocytogenes (MICs within a range of 25-30 μg/ml) and moderate activity against four Gram-negative bacteria Salmonella typhimurium, Escherichia coli, Pseudomonas aeruginosa, and Pantoea ananatis (MICs within a range of 30-100 μg/ml). The plant pathogenic bacterium P. ananatis and human pathogenic S. typhimurium responded at comparatively higher concentrations of the compound 1, which were 75 and 100 μg/ml respectively. The compound inhibited the growth of Gram-positive B. subtilis and Gram-negative P. aeruginosa completely with a clear bactericidal mode of action at their MIC values. The compound upon treatment on both B. subtilis and P. aeruginosa released substantial amount of nucleic acid in the external medium and also effected the change of morphology towards pleomorphicity, thereby indicating its probable action on cell membrane. Furthermore, the triterpenoid 1 was found not to inhibit a probiotic lactic acid bacterium Lactococcus lactis subsp. lactis LABW4 under in vitro condition and to possess no toxicity in Swiss albino mice.

Enzymes of carbohydrate metabolism in root‐nodule bacteria during growth on acetate

The key enzymes of the Embden‐Meyerhof‐Parnas (EMP), Entner‐Doudoroff (ED) and pentose phosphate (PP) pathways as well as those of the tricarboxylic acid (TCA) cycle and gluconeogenesis were assayed in the cells of Rhizobium and Bradyrhizobium grown on acetate. Except for glyceraldehyde‐3‐phosphate dehydrogenase, the activities of all the enzymes of the EMP, ED and PP pathways were found to be low in acetate grown cells in the present study as compared to those of glucose grown cells reported by us earlier (Mandal and Chakrabartty 1993) indicating a probable repression of the enzymes. The enzymes of the tricarboxylic acid cycle were detected in high levels in the acetate grown cells of the root‐nodule bacteria. The operation of the glyoxylate pathway for acetate metabolism in the root‐nodule bacteria were reported previously by us (Mandal and Chakrabartty 1992). The evidences taken together point to the simultaneous operation of both the TCA cycle and the glyoxylate cycle for acetate metabolism in these bacteria.

New Health Potentials of Orally Consumed Probiotic Microorganisms

The microorganism and their live formulations upon consumption contribute to intestinal microbial balance are known as probiotics. They generally live in our gut mucosal layer and also in some other body parts like mouth, vagina and offer a number of health benefits to the host. They fight with the invading pathogens by producing a number of active principles like bacteriocins or by other mechanisms and kill or outnumber them. These probiotic organisms not only fight with the pathogens of the host but also contribute a lot in improving the immunological and physiological state of the host by interfering their metabolic processes. As they colonize in vital parts of human intestine, they intricately involve with different systems of human body and alleviate the problem associated with them. The major probiotic organisms used today are the species of Lactobacillus, Bifidobacterium, Enterococcus, Pediococcus, etc. In this chapter how different strains or species of such orally consumed probiotic organisms could offer different kinds of health benefits particularly in relation to modulation of immunological parameters, allergy, and lung emphysema are discussed with very recent references.

Change of Carbon Metabolic Activity of Rhizobium Under Carbon Starvation

One fast growing strain of Rhizobium sp (Vigna mungo) VBS 1 was tested for its metabolic activities under carbon starvation. Specific activities of the catabolic enzymes like phosphofructokinase, fructose-1,6-bisphosphate aldolase, iso-citrate dehydrogenase and malate dehydrogenase decreased remarkably whereas, induction of two anapleurotic enzymes like fructose-1,6-bisphosphatase and iso-citrate lyase took place in the cell-free extract of the strain. Almost unchanged specific activity of the enzyme glyceraldehyde-3-phosphate dehydrogenase indicated its key role in maintaining a balance between catabolic and anabolic activities under carbon starvation.