Notch Activation Is Dispensable for D, L-Sulforaphane-Mediated Inhibition of Human Prostate Cancer Cell Migration

D, L-Sulforaphane (SFN), a synthetic racemic analog of broccoli constituent L-sulforaphane, is a highly promising cancer chemopreventive agent with in vivo efficacy against chemically-induced as well as oncogene-driven cancer in preclinical rodent models. Cancer chemopreventive effect of SFN is characterized by G2/M phase cell cycle arrest, apoptosis induction, and inhibition of cell migration and invasion. Moreover, SFN inhibits multiple oncogenic signaling pathways often hyperactive in human cancers, including nuclear factor-κB, Akt, signal transducer and activator of transcription 3, and androgen receptor. The present study was designed to determine the role of Notch signaling, which is constitutively active in many human cancers, in anticancer effects of SFN using prostate cancer cells as a model. Exposure of human prostate cancer cells (PC-3, LNCaP, and/or LNCaP-C4-2B) to SFN as well as its naturally-occurring thio-, sulfinyl-, and sulfonyl-analogs resulted in cleavage (activation) of Notch1, Notch2, and Notch4, which was accompanied by a decrease in levels of full-length Notch forms especially at the 16- and 24-hour time points. The SFN-mediated cleavage of Notch isoforms was associated with its transcriptional activation as evidenced by RBP-Jk-, HES-1A/B- and HEY-1 luciferase reporter assays. Migration of PC-3 and LNCaP cells was decreased significantly by RNA interference of Notch1 and Notch2, but not Notch4. Furthermore, SFN-mediated inhibition of PC-3 and LNCaP cell migration was only marginally affected by knockdown of Notch1 and Notch2. Strikingly, SFN administration to Transgenic Adenocarcinoma of Mouse Prostate transgenic mice failed to increase levels of cleaved Notch1, cleaved Notch2, and HES-1 proteins in vivo in prostatic intraepithelial neoplasia, well-differentiated carcinoma or poorly-differentiated prostate cancer lesions. These results indicate that Notch activation is largely dispensable for SFN-mediated inhibition of cell migration, which should be viewed as a therapeutic advantage as Notch activation is frequent in human prostate cancers. © 2012 Hahm et al

Evaluation of some effective potentialities of newly formulated rice fermented food using Elephantopus scaber L. rhizome as herbal starter

Traditionally, fermented food and beverages are prepared by adding a mixture of plant residues as a starter or source of microbes. Most of the conventional fermented foods use a local starter which contains a mixture of herbs or old ferment or otherwise cereal dust-coated tablet. In this study, we have made an attempt to prepare a rice-based fermented food with the herbal starter (0.5% w/w) of Elephantopus scaber L. rhizome, and also examined its microbial and nutrient profiles. The food product is fortified with organic acid and titratable acidity of 0.58% and also contained an excellent source of microbes (LAB and Bifidobacterium sp.). The fermented food contains significant amount of fat, protein, minerals, vitamins, oligosaccharide, unsaturated fatty acids (ω3, ω6, ω7 and ω9) and a pool of free amino acids. The presence of phytochemical contents in the fermented rice was also exhibited significant effects against commercially available free radicals (DPPH, ABTS, FRAP and OH-radicals). Thus, food-grade microbes containing newly formulated fermented food would provide essential macro-and micro-nutrients to the individuals and convey the sustainability of good health. Therefore, the mentioned plant part would be used as an effective starter for aiding rice-based food products

Dietotherapeutic potency of ornamental lentil dumpling, a traditional food preparation from South West Bengal, India

Gahana bori (in Bengali) or ornamental lentil dumpling is a state-of-art preparation designed in the form of paisleys, ornaments or flowers, used as a decorative adjunct with the main dish.. Here, we have made an attempt to evaluate the dirtotherapeutic potency of this traditional preparation. The principal ingredient is the Vigna mungo (blackgram/ urad bean). In its preparation, the soaked bean is pasted and placed on a cloth piece having a central small pore. The fermented paste is squeezed onto the poppy seeds containing plate in such a way that it looks like an ornament. The sundried preparation is generally fried in oil and served along with the meal. For the first time, we have scientifically explored Gahana bori. The number of total aerobes, total anaerobes, yeast, mould, and LAB were increased during soaking. The contents of free phenolics and flavonoids were increased in the fermented paste and that also reflected by the higher in vitro DPPH antioxidant activity. The levels of B-group of vitamins particularly the quantity of riboflavin, thiamin, folic acid, vitamin B12, and vitamin C were also enriched in the products. The water extract of this product exhibited a notable antibacterial activity against enteropathogens. Thus, the lentil-based Gahana bori is not only improved the appearance or presentation of food product but also the same have a good health beneficial potentiality

Ethnic Preparation of Haria, a Rice-Based Fermented Beverage, in the Province of Lateritic West Bengal, India

Haria is a rice-based fermented beverage that is popular among tribal and low income people in lateritic West Bengal and East-Central India. The principal ingredient of this beverage is low grade boiled rice (Oryza sativa L.), which is mixed with a traditional starter, called bakhar, and fermented within a heat-sterilized earthen pot for 3-4 days. The main aim of this study was to investigate the ethnobotanical importance and traditional process of haria preparation. The method adopted for this study was based on interactive questionnaires and laboratory experiments. It was found that the pH decreased during the course of fermentation with increased titratable acidity of 1.42%. The alcohol content was 2-3% (v/v) in the consumable beverages. This documentation will be useful for further exploitation of haria as a health drink

Type IIP Supernova SN 2004et: A Multi-Wavelength Study in X-Ray, Optical and Radio

We present X-ray, broad band optical and low frequency radio observations of the bright type IIP supernova SN 2004et. The \cxo observed the supernova at three epochs, and the optical coverage spans a period of $\sim$ 470 days since explosion. The X-ray emission softens with time, and we characterise the X-ray luminosity evolution as \Lx \propto t^{-0.4}. We use the observed X-ray luminosity to estimate a mass-loss rate for the progenitor star of \sim \ee{2}{-6} M_\odot \mathrm{yr}^{-1}. The optical light curve shows a pronounced plateau lasting for about 110 days. Temporal evolution of photospheric radius and color temperature during the plateau phase is determined by making black body fits. We estimate the ejected mass of $^{56}$Ni to be 0.06 $\pm$ 0.03 M$_\odot$. Using the expressions of Litvinova & Nad\"{e}zhin (1985) we estimate an explosion energy of (0.98 $\pm$ 0.25) $\times 10^{51}$ erg. We also present a single epoch radio observation of SN 2004et. We compare this with the predictions of the model proposed by Chevalier et al. (2006). These multi-wavelength studies suggest a main sequence progenitor mass of $\sim$ 20 M$_\odot$ for SN 2004et.Comment: 13 Figures, Accepted for Publication in MNRA

Optical Observations of GRB 050401 Afterglow : A case for Double Jet Model

The afterglow of GRB 050401 presents several novel and interesting features : [1] An initially faster decay in optical band than in X-rays. [2] A break in the X-ray light curve after $\sim$ 0.06 day with an unusual slope after the break. [3] The X-ray afterglow does not show any spectral evolution across the break while the R band light curve does not show any break. We have modeled the observed multi-band evolution of the afterglow of GRB 050401 as originating in a two component jet, interpreting the break in X-ray light curve as due to lateral expansion of a narrow collimated outflow which dominates the X-ray emission. The optical emission is attributed to a wider jet component. Our model reproduces all the observed features of multi-band afterglow of GRB 050401. We present optical observations of GRB 050401 using the 104-cm Sampurnanand Telescope at ARIES, Nainital. Results of the analysis of multi-band data are presented and compared with GRB 030329, the first reported case of double jet.Comment: 8 pages, 2 figures and 4 tables. To appear in MNRA

Curative Effect of 18β-Glycyrrhetinic Acid in Experimental Visceral Leishmaniasis Depends on Phosphatase-Dependent Modulation of Cellular MAP Kinases

We earlier showed that 18β-glycyrrhetinic acid (GRA), a pentacyclic triterpenoid from licorice root, could completely cure visceral leishmaniasis in BALB/c mouse model. This was associated with induction of nitric oxide and proinflammatory cytokine production through the up regulation of NF-κB. In the present study we tried to decipher the underlying cellular mechanisms of the curative effect of GRA. Analysis of MAP kinase pathways revealed that GRA caused strong activation of p38 and to a lesser extent, ERK in bone marrow-derived macrophages (BMDM). Almost complete abrogation of GRA-induced cytokine production in presence of specific inhibitors of p38 and ERK1/2 confirmed the involvement of these MAP kinases in GRA-mediated responses. GRA induced mitogen- and stress-activated protein kinase (MSK1) activity in a time-dependent manner suggested that GRA-mediated NF-κB transactivation is mediated by p38, ERK and MSK1 pathway. As kinase/phosphatase balance plays an important role in modulating infection, the effect of GRA on MAPK directed phosphatases (MKP) was studied. GRA markedly reduced the expression and activities of three phosphatases, MKP1, MKP3 and protein phosphatase 2A (PP2A) along with a substantial reduction of p38 and ERK dephosphorylation in infected BMDM. Similarly in the in vivo situation, GRA treatment of L. donovani-infected BALB/c mice caused marked reduction of spleen parasite burden associated with concomitant decrease of individual phosphatase levels. However, activation of kinases also played an important role as the protective effect of GRA was significantly abrogated by pharmacological inhibition of p38 and ERK pathway. Curative effect of GRA may, therefore, be associated with restoration of proper cellular kinase/phosphatase balance, rather than modulation of either kinases or phosphatases

Plasmid-Cured Chlamydia caviae Activates TLR2-Dependent Signaling and Retains Virulence in the Guinea Pig Model of Genital Tract Infection

Loss of the conserved “cryptic” plasmid from C. trachomatis and C. muridarum is pleiotropic, resulting in reduced innate inflammatory activation via TLR2, glycogen accumulation and infectivity. The more genetically distant C. caviae GPIC is a natural pathogen of guinea pigs and induces upper genital tract pathology when inoculated intravaginally, modeling human disease. To examine the contribution of pCpGP1 to C. caviae pathogenesis, a cured derivative of GPIC, strain CC13, was derived and evaluated in vitro and in vivo. Transcriptional profiling of CC13 revealed only partial conservation of previously identified plasmid-responsive chromosomal loci (PRCL) in C. caviae. However, 2-deoxyglucose (2DG) treatment of GPIC and CC13 resulted in reduced transcription of all identified PRCL, including glgA, indicating the presence of a plasmid-independent glucose response in this species. In contrast to plasmid-cured C. muridarum and C. trachomatis, plasmid-cured C. caviae strain CC13 signaled via TLR2 in vitro and elicited cytokine production in vivo similar to wild-type C. caviae. Furthermore, inflammatory pathology induced by infection of guinea pigs with CC13 was similar to that induced by GPIC, although we observed more rapid resolution of CC13 infection in estrogen-treated guinea pigs. These data indicate that either the plasmid is not involved in expression or regulation of virulence in C. caviae or that redundant effectors prevent these phenotypic changes from being observed in C. caviae plasmid-cured strains