Incidence of white muscle disease, a viral like disease associated with mortalities in hatchery reared postlarvae of the giant freshwater prawn Macrobrachium rosenbergii (De Man) from the south east coast of India

Incidence of post-larval mortalities of 30- 100% was reported from commercial freshwater prawn Macrobrachium rosenbergii (De Man) hatcheries in Andhra Pradesh and Tamil Nadu (south-eastern states of India) since 2001. Infec ted postlarvae (PL) exhibited clinical symptoms with lethargy, anorexia and whitening of abdominal muscles and the disease was identified as white muscle disease (WMD)

Involvement of Enterobacter cloacae in the mortality of the fish, Mugil cephalus

Enterobacter cloacae, an enteric bacterium that belongs to the family Enterobacteriaceae, is widely distributed in nature. It is found in faeces of humans and animals, water, soil, plants, plant materials, insects and dairy product

Monitoring the Antioxidant Mediated Chemosensitization and ARE-Signaling in Triple Negative Breast Cancer Therapy

<div><p>Chemotherapy often fails due to cellular detoxifying mechanisms, including phase-II enzymes. Activation of Nrf2-Keap1 pathway induces phase-II enzymes expression through ARE-signaling and prevents cancer development. Nrf2-overexpression in cancer cells results in chemo- and/or radioresistance. This necessitates understanding of Nrf2-regulation, and identification of Nrf2 activators/inhibitors sensitizing cancer cells to improve chemotherapy. N-terminal 435-amino acids of Nrf2 are crucial for Keap1 binding during ubiquitination. Identification of a minimum Nrf2-domain required for Keap1 binding without altering endogenous ARE-signaling would be a novel tool to study Nrf2-signaling. Current study developed firefly-luciferase reporter fusion with N-terminal Nrf2-domain of different lengths and examined its response to Nrf2-activators in cells. The results identified FLuc2 fusion with N-terminal 100-aa of Nrf2 is sufficient for measuring Nrf2-activation in cancer cells. We used MDA-MB231 cells expressing this particular construct for studying antioxidant induced Nrf2-activation and chemosensitization in triple-negative breast cancer therapy. While antioxidant EGCG showed chemosensitization of MDA-MB231 cells to cisplatin by activating Nrf2-ARE signaling, PTS, another antioxidant showed chemoprotection. Tumor xenograft study in mouse demonstrates that combinational treatment by cisplatin/EGCG resulted in tumor growth reduction, compared to cisplatin alone treatment. The results of this study highlight the importance of identifying selective combination of antioxidants/chemotherapeutic agents for customized treatment strategy.</p></div

Formulation of Anti-miR-21 and 4‑Hydroxytamoxifen Co-loaded Biodegradable Polymer Nanoparticles and Their Antiproliferative Effect on Breast Cancer Cells

Breast cancer is the second leading cause of cancer-related death in women. The majority of breast tumors are estrogen receptor-positive (ER+) and hormone-dependent. Neoadjuvant anti-estrogen therapy has been widely employed to reduce tumor mass prior to surgery. Tamoxifen is a broadly used anti-estrogen for early and advanced ER+ breast cancers in women and the most common hormone treatment for male breast cancer. 4-Hydroxytamoxifen (4-OHT) is an active metabolite of tamoxifen that functions as an estrogen receptor antagonist and displays higher affinity for estrogen receptors than that of tamoxifen and its other metabolites. MicroRNA-21 (miR-21) is a small noncoding RNA of 23 nucleotides that regulates several apoptotic and tumor suppressor genes and contributes to chemoresistance in numerous cancers, including breast cancer. The present study investigated the therapeutic potential of 4-OHT and anti-miR-21 coadministration in an attempt to combat tamoxifen resistance, a common problem often encountered in anti-estrogen therapy. A biodegradable poly­(d,l-lactide-<i>co</i>-glycolide)-<i>block</i>-poly­(ethylene glycol) (PLGA-<i>b</i>-PEG-COOH) copolymer was utilized as a carrier to codeliver 4-OHT and anti-miR-21 to ER+ breast cancer cells. 4-OHT and anti-miR-21 co-loaded PLGA-<i>b</i>-PEG nanoparticles (NPs) were developed using emulsion-diffusion evaporation (EDE) and water-in-oil-in-water (w/o/w) double emulsion methods. The EDE method was found to be best method for 4-OHT loading, and the w/o/w method proved to be more effective for coloading NPs with anti-miR-21 and 4-OHT. The optimal NPs, which were prepared using the double emulsion method, were evaluated for their antiproliferative and apoptotic effects against MCF7, ZR-75-1, and BT-474 human breast cancer cells as well as against 4T1 mouse mammary carcinoma cells. We demonstrated that PLGA-<i>b</i>-PEG NP encapsulation significantly extended 4-OHT’s stability and biological activity compared to that of free 4-OHT. MTT assays indicated that treatment of MCF7 cells with 4-OHT–anti-miR-21 co-loaded NPs resulted in dose-dependent antiproliferative effects at 24 h, which was significantly higher than what was achieved with free 4-OHT at 48 and 72 h post-treatment. Cell proliferation analysis showed that 4-OHT and anti-miR-21 co-loaded NPs significantly inhibited MCF-7 cell growth compared to that of free 4-OHT (1.9-fold) and untreated cells (5.4-fold) at 1 μM concentration. The growth rate of MCF7 cells treated with control NPs or NPs loaded with anti-miR-21 showed no significant difference from that of untreated cells. These findings demonstrate the utility of the PLGA-<i>b</i>-PEG polymer NPs as an effective nanocarrier for co-delivery of anti-miR-21 and 4-OHT as well as the potential of this drug combination for use in the treatment of ER+ breast cancer

Effect of anticancer drugs in response to antioxidant-Nrf2-activators in MDA-MB231 cells.

<p>Apoptotic effect of anticancer drug RRx-001 (2.5 μM) in response to antioxidants EGCG (0–50 μM) (A) and PTS (0–10 μM) (B). C, Effect of GSH pathway inhibitor sulfasalazine on apoptotic rates of cells treated with anticancer drug RRx-001 (2.5 μM) with or without EGCG (0–50 μM). Error bars represent standard deviations of triplicate experiments.</p

Time (A) and concentration (B) dependent activation of Nrf2-100-FLuc2 fusions in response to Nrf2-activators in cells.

<p>Asterisk (*) denotes statistical significance (p<0.05) compared to DMSO control (A) and non-exposed cells control (B). Expression of antioxidant genes in response to Nrf2 activators in MDA-MB231 cells stably expressing Nrf2-100aa-FLuc2 fusion. C, Immunoblot analysis of Nrf2, NQO1 and GST expression normalized to GAPDH expression and to control sample. The images were acquired by optical CCD (IVIS) camera imaging. Error bars represent SEM (A, B) or standard deviations (C) of triplicate experiments.</p

Time dependent activation of Nrf2-100-FLuc2 fusions in response to varying anticancer drug (A, RRx-001 and B, cisplatin) concentration in the presence of antioxidant (EGCG) in MDA-MB231 cells, and Nrf2 target genes (GST and NQO1) expression in MDA-MB231-Nrf2-100-FLuc2 cells in response to anticancer drug (RRx-001) in the presence of antioxidant (EGCG).

<p>Asterisk (*) denotes statistical significance (p<0.05) of a signal compared to that from the untreated cells (A) and from cells treated with 50 μM EGCG alone (B). C, Immunoblot of cell lysates treated with drug and/or antioxidant for 24 hours (Nrf2, GST and NQO1 expression was normalized to GAPDH expression). Error bars represent standard deviations of triplicate experiments.</p

Review Therapeutic Evaluation of microRNAs by Molecular Imaging

licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. Received: 2013.07.26; Accepted: 2013.09.22; Published: 2013.12.06 MicroRNAs (miRNAs) function as regulatory molecules of gene expression with multifaceted activities that exhibit direct or indirect oncogenic properties, which promote cell proliferation, differentiation, and the development of different types of cancers. Because of their extensive functional involvement in many cellular processes, under both normal and pathological conditions such as various cancers, this class of molecules holds particular interest for cancer research. MiRNAs possess the ability to act as tumor suppressors or oncogenes by regulating the expression of different apoptotic proteins, kinases, oncogenes, and other molecular mechanisms that can cause the onset of tumor development. In contrast to current cancer medicines, miRNA-based therapies function by subtle repression of gene expression on a large number of oncogenic factors, and therefore are anticipated to be highly efficacious. Given their unique mechanism of action, miRNAs are likely to yield a new class of targeted therapeutics for a variety of cancers. More than thousand miRNAs have been identified to date, and their molecular mechanisms and functions ar