Arsenic and its various forms have been in use in ancient Chinese medicine for more than 2000 years. Arsenicals have gained importance for having remedial effects for various diseases from syphilis to cancer thus highlighting its role as a therapeutic agent even though it has been labelled as a potential 'poison'. The ability of arsenic, specifically arsenic trioxide, to treat acute promyelocytic leukaemia has radically changed the perception of this poison and has been the main factor for the re-emergence of this candidate to Western medicine for the treatment of leukaemia and other solid tumours. This review highlights the glorious history of arsenic and its various forms with major emphasis on arsenic trioxide as a therapeutic agent. The mechanism of action, pathogenesis, pharmacokinetic profile, safety concerns, ongoing clinical trials and various new forms of arsenic trioxide are discussed. The review also outlines the therapeutic ability of this drug, discusses the latest developments and recent investigations and potential advancement of arsenic trioxide as nanoformulations that has made it emerge as a potential remedial agent.

Nucleolin is an abundant multifunctional nucleolar protein with defined roles in ribosomal RNA processing, RNA polymerase I-catalyzed transcription, and the regulation of apoptosis. Earlier we reported that human nucleolin binds to the p53-antagonist Hdm2 as determined by reciprocal co-immunoprecipitation assays using cell lysates. We also demonstrated that nucleolin antagonizes Hdm2-mediated degradation of p53. Here, we identify specific domains of nucleolin and Hdm2 proteins that support mutual interaction and investigated the implications of complex formation on p53-ubiquitination and protein levels. Our data indicate that the nucleolin N-terminus as well as the central RNA-binding domain (RBD) are predominantly involved in binding to Hdm2. The nucleolin RBD robustly bound to the NLS/NES (nuclear localization and export signals) domain of Hdm2 in vitro, while N-terminus of nucleolin preferentially associated with the Hdm2 RING domain expressed in cells. We further demonstrate that the C-terminal GAR (Glycine-Arginine Rich) domain of nucleolin serves as the predominant binding domain for direct interaction with p53. While over-expression of nucleolin or its various domains had no significant effect on Hdm2 auto-ubiquitination, the nucleolin RBD antagonized the Hdm2 E3 ligase activity against p53, leading to p53 stabilization. Conversely, the adjacent GAR domain of nucleolin interacted with p53 causing a modest stimulatory effect on p53 ubiquitination. These data suggest that changes in nucleolin conformation can alter the availabilities of such domains in vivo to modulate the overall impact of nucleolin on Hdm2 activity and hence on p53 stability.

OVGP1 is specifically induced in the luminal epithelium at the time of embryo implantation where it regulates receptivity-related genes and aids in trophoblast adhesion.

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Allergic diseases, such as allergic asthma, are hypersensitivity reactions initiated by immunological mechanisms. Myrica esculenta (M. esculenta) is known traditionally in Ayurveda to possess anti-asthmatic activity. The present investigation was undertaken to evaluate the effect of crude extract of stem bark of M. esculenta (Family Myricaceae, commonly known as Kaiphal) on experimental allergic reactions. Experimental models studied were allergic pleurisy and vascular permeability induced by acetic acid in mice. Pretreatment with M. esculenta (75 mg/kg and 150 mg/kg, p.o.) significantly inhibited the eosinophil accumulation (P < 0.01) respectively in the pleural cavity. M. esculenta (75 and 150 mg/kg, p.o.) significantly inhibited the rise in plasma exudation (57.12% and 59.77%, P < 0.01) induced by acetic acid in mice. These findings demonstrate that the crude extract from the stem bark of M. esculenta possesses antiallergic activity. This activity may be mediated by reducing the release of mediators such as histamine, inhibition of mast cell degranulation, and inhibition of eosinophil accumulation thereby preventing the release of cytokines and chemokines.

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The secretory cells lining the lumen of the mammalian oviduct synthesize and secrete high molecular weight glycoprotein (OGP). Molecular cDNA cloning of most of the mammalian OGP has been accomplished. The nucleotide and deduced amino acid sequences show a remarkable homology across species and also to chitinase protein. Even though OGP has been shown to interact with gametes and the early embryo, the protein's direct function has not yet been established. A prerequisite for such studies is the availability of well-characterized protein in bulk. We used recombinant DNA technology to obtain OGP (rOGP). An authentic partial cDNA clone encoding bonnet monkey (Macaca radiata) OGP (accession number AF132 215) was recloned into expression vector pET20b. Overexpression of the protein could be demonstrated after induction with isopropylthio-beta-galactopyranoside. Recombinant protein was purified by gel filtration of Escherichia coli lysate through Sephadex G75. The protein migrated with a molecular weight of approximately 14 kDa on SDS-PAGE. The molecular weight as assessed by matrix-assisted laser adsorption time-of-flight was 14 439 daltons. With Western blot procedures the protein could be immunostained with antibodies to human OGP, baboon OGP, and antipeptide antibodies generated against a well-conserved region of mammalian OGP. The monospecificity of rabbit antibodies generated against rOGP was established by its ability to immunostain human OGP (100-110 kDa) isolated from hydrosalpinx by Western blot analysis, and the antibody immunostained epithelial cells that secrete OGP in human fallopian tubes. OGP binding sites on the head and tail region of monkey sperm could be demonstrated by using antibody against rOGP.

Background:The exposure of skin to ultraviolet-B (UV-B) radiations leads to deoxyribonucleic acid (DNA) damage and can induce production of free radicals which imbalance the redox status of the cell and lead to increased oxidative stress. Clove has been traditionally used for its analgesic, anti-inflammatory, anti-microbial, anti-viral, and antiseptic effects.Objective:To evaluate the UV-B protective activity of flavonoids from Eugenia caryophylata (clove) buds on human dermal fibroblast cells.Materials and Methods:Protective ability of flavonoid-enriched (FE) fraction of clove was studied against UV-B induced cytotoxicity, anti-oxidant regulation, oxidative DNA damage, intracellular reactive oxygen species (ROS) generation, apoptotic morphological changes, and regulation of heme oxygenase-1 (HO-1) gene through nuclear factor E2-related factor 2 antioxidant response element (Nrf2 ARE) pathway.Results:FE fraction showed a significant antioxidant potential. Pretreatment of cells with FE fraction (10–40 μg/ml) reversed the effects of UV-B induced cytotoxicity, depletion of endogenous enzymatic antioxidants, oxidative DNA damage, intracellular ROS production, apoptotic changes, and overexpression of Nrf2 and HO-1.Conclusion:The present study demonstrated for the first time that the FE fraction from clove could confer UV-B protection probably through the Nrf2-ARE pathway, which included the down-regulation of Nrf2 and HO-1. These findings suggested that the flavonoids from clove could potentially be considered as UV-B protectants and can be explored further for its topical application to the area of the skin requiring protection.SUMMARY Pretreatment of human dermal fibroblast with flavonoid-enriched fraction of Eugenia caryophylata attenuated effects of ultraviolet-B radiationsIt also conferred protection through nuclear factor E2-related factor 2-antioxidant response pathway and increased tolerance of cells against oxidative stressFlavonoid-enriched fraction can be explored further for topical application to the skin as a ultraviolet-B protectant. Abbreviations used: ABTS: 2,2’-azino-bis-(3-ethylbenzothiazoline- 6-sulphonic acid), AO: Acridine orange, ANOVA: Analysis of variance, ARE: Antioxidant response elements, BSA: Bovine serum albumin, CAPE: Caffeic acid phenethyl ester, CAT: Catalase, DCFH-DA: 2’,7’-dichlorofluorescein diacetate, DMEM: Dulbecco's Modified Eagle's Medium, DMSO: Dimethyl sulfoxide, DNA: Deoxyribonucleic acid, DPBS: Dulbecco's phosphate buffered saline, DPPH: 2,2-diphenyl-1-picrylhydrazyl, ECL: Enhanced chemiluminescence, EDTA: Ethylenediaminetetraacetic acid, ELISA: Enzyme-linked immunesorbent assay, EtBr: Ethidium bromide, FBS: Fetal bovine serum, FE fraction: Flavonoid-enriched fraction, FRAP: Ferric reducing antioxidant power, GPx: Glutathione peroxidase, GR: Glutathione reductase, GST: Glutathione-S-transferase, GSH: Reduced glutathione, GSSG: Oxidized glutathione, HDF: Human dermal fibroblast, HEPES: 4-(2-hydroxyethyl)-1-piperazineethanesulphonic acid, HRP: Horseradish peroxidase, HO-1: Hem...