The curcumin analog HO-3867 selectively kills cancer cells by converting mutant p53 protein to transcriptionally active wildtype p53.

p53 is an important tumor-suppressor protein that is mutated in more than 50% of cancers. Strategies for restoring normal p53 function are complicated by the oncogenic properties of mutant p53 and have not met with clinical success. To counteract mutant p53 activity, a variety of drugs with the potential to reconvert mutant p53 to an active wildtype form have been developed. However, these drugs are associated with various negative effects such as cellular toxicity, nonspecific binding to other proteins, and inability to induce a wildtype p53 response in cancer tissue. Here, we report on the effects of a curcumin analog, HO-3867, on p53 activity in cancer cells from different origins. We found that HO-3867 covalently binds to mutant p53, initiates a wildtype p53-like anticancer genetic response, is exclusively cytotoxic toward cancer cells, and exhibits high anticancer efficacy in tumor models. In conclusion, HO-3867 is a p53 mutant-reactivating drug with high clinical anticancer potential.

Two epizootic Perkinsus spp. events in commercial oyster farms at Santa Catarina, Brazil.

Perkinsus spp. have been detected in various bivalve species from north-east Brazil. Santa Catarina is a South Brasil state with the highest national oyster production. Considering the pathogenicity of some Perkinsus spp., a study was carried out to survey perkinsosis in two oyster species cultured in this State, the mangrove oyster Crassostrea gasar and the Pacific oyster Crassostrea gigas. Sampling involved eight sites along the state coast, and oyster sampling was collected during the period between January 2013 and December 2014. For the detection of Perkinsus, Ray's fluid thioglycollate medium (RFTM) and histology were used, and for the identification of the species, PCR and DNA sequencing were used. Perkinsus spp. was found by RFTM in C. gigas and C. gasar from São Francisco do Sul. This pathology was also detected in C. gasar from Balneário Barra do Sul both, by RFTM and histology. Perkinsus marinus was identified in C. gigas and C. gasar from São Francisco do Sul and Perkinsus beihaiensis in C. gasar from Balneário Barra do Sul. This is the first report of P. marinus in C. gigas from South America. Results of this preliminary study suggest that both oyster species tolerate the species of Perkinsus identified, without suffering heavy lesions.

Twin anemia polycythemia sequence: a report of three cases.

BACKGROUND: Vascular anastomoses in monochorionic placentas are the key factor in the develop- ment of several complications, including twin anemiapolycythemia sequence (TAPS). TAPS is an uncommon form of chronic fetofetal transfusion, characterized by large intertwin hemoglobin (Hb) differences in the absence of amniotic fluid discordances. CASE: We report 3 unusual cases of spontaneous TAPS. Looking to the intertwin Hb differences, each case fits in a different stage of postnatal twin anemia-polycythemia classification. Five of the 6 twins had a good outcome despite major hemodynamic changes. CONCLUSION: Spontaneous TAPS is by far more infrequent than its postlaser counterpart. Our report is somewhat uncommon due to the fact that the 3 cases were spontaneous, consecutive, and each one fit as an example of the various degrees of severity according to the described classifications of this condition.

The potential of Apiaceae species as sources of singular phytochemicals and plant-based pesticides.

The Apiaceae Lindl. (=Umbelliferae Juss.), which includes several economical important vegetables, herbs, and spices, is one of the most numerous plant family. Umbelliferous crops (namely anise, fennel, carrot, coriander, parsley, etc.) are also valuable sources of botanical flavoring agents and fragrances. In addition, Apiaceae species yield a wide variety of distinctive specialized metabolites (i.e, volatile phenylpropanoids, furanocoumarins, sesquiterpene coumarins, polyacetylenes, and phthalides), some of them been described as uncommon natural phytochemicals exclusive of the family, which offers a great potential for bioprospection. Numerous studies have pointed out the outstanding biological activity of extracts and several classes of phytochemicals from Apiaceae species. Emphasis has been given to essential oils (EOs) and their constituents activities, most likely because this type of plant added value product benefits from a larger acceptance and application potential in integrated pest management (IPM) and integrated vector management (IVM) programs. Several species of the family offer a variety of unique compounds with great potential as biopesticidal and/or synergizing agents. Investigations covering their activity toward agricultural pests and phytopathogens have increased in the last years, nevertheless the interest remains strongly focus on arthropod species, predominantly those acting as vectors of human diseases. From our survey, it is patent the gap of knowledge concerning the potential molluscicidal properties of Apiaceae extracts/phytochemicals, as well as their herbicidal activities against invasive plant species. In this review, we propose to highlight the potential of Apiaceae species as suitable sources of bioactive phytochemicals with great relevance within the frame of plant-based pesticides R&D, and will discuss their applicability in real-world scenarios considering the recent developments regarding the design of stable formulations incorporating Apiaceae bioactive products. We expect that this review will encourage researchers to consider undervalued Apiaceae species as alternative sources of bioactive compounds and will give a contribute to the field by suggesting new research topics.

The influence of heavy metals on toxicogenetic damage in a Brazilian tropical river.

Anthropogenic activities in tropical rivers favor the eutrophication process, which causes increased concentration of heavy metals. The presence and bioaccumulation of metals are directly related to the presence of genotoxic damage in aquatic organisms. Thus, we evaluated the presence of heavy metals (Fe, Zn, Cr, Cu and Al) and performed toxicogenetic tests in surface (S) and bottom (B) of water samples of the Poti river (Piaui/Brazil). Cytotoxicity and genotoxicity tests were performed in Allium cepa, and micronucleus (MN) and comet assay were performed in Oreochromis niloticus. The chemical analysis showed concentrations above the limit for Cu, Cr, Fe and Al according to Brazilian laws, characterizing anthropogenic disturbance in this aquatic environment. Toxicogenetic analysis presented significant cytotoxic, mutagenic and genotoxic effects in different exposure times and water layers (S and B), especially alterations in mitotic spindle defects, MN formations, nuclear bud and DNA strand breaks. Correlations between Fe and cytotoxicity, and Al and mutagenicity were statistically significant and point out to the participation of heavy metals in genotoxic damage. Therefore, Poti river water samples presented toxicogenetic effects on all bioindicators analyzed, which are most likely related to heavy metals pollution.

Tissue-specificity of prostate specific antigens: comparative analysis of transcript levels in prostate and non-prostatic tissues.

Activation of immune defense mechanisms against tumor antigens appears to be a promising therapeutic option for advanced prostate cancer (PCa). Specific immunotherapy critically depends on target antigens that are selectively expressed in the tumorous and optional in the normal prostate tissue in sufficient amounts. Although several prostate antigens have been described and some have already been used in clinical trials, a detailed comparative evaluation of their tissue-specificity and expression levels is still lacking. We determined the transcript levels of eight prostate targets (PSA, PAP, PSCA, PSGR, Prostein, PSMA, AIbZIP, trp-p8) in 16 different tissues by quantitative PCR and calculated a tissue-specificity index (TSI) for each molecule. Besides a preferential expression in prostate for all targets, striking differences in the expression levels and TSI were revealed which may be important for the selection of appropriate antigens for immunotherapy of PCa.

The microglial α7-acetylcholine nicotinic receptor is a key element in promoting neuroprotection by inducing heme oxygenase-1 via nuclear factor erythroid-2-related factor 2.

AIMS: We asked whether the neuroprotective effect of cholinergic microglial stimulation during an ischemic event acts via a mechanism involving the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) and/or the expression of its target cytoprotective gene, heme oxygenase-1 (HO-1). Specifically, the protective effect of the pharmacologic alpha-7 nicotinic acetylcholine receptor (α7 nAChR) agonist PNU282987 was analyzed in organotypic hippocampal cultures (OHCs) subjected to oxygen and glucose deprivation (OGD) in vitro as well as in photothrombotic stroke in vivo. RESULTS: OHCs exposed to OGD followed by reoxygenation elicited cell death, measured by propidium iodide and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide staining. Activation of α7 nAChR by PNU282987, after OGD, reduced cell death, reactive oxygen species production, and tumor necrosis factor release. This was associated with induction of HO-1 expression, an effect reversed by α-bungarotoxin and by tin-protoporphyrin IX. The protective effect of PNU282987 was lost in microglial-depleted OHCs as well as in OHCs from Nrf2-deficient-versus-wild-type mice, an effect associated with suppression of HO-1 expression in microglia. Administration of PNU282987 1 h after induction of photothrombotic stroke in vivo reduced the infarct size and improved motor skills in Hmox1(lox/lox) mice that express normal levels of HO-1, but not in LysM(Cre)Hmox1(Δ/Δ) in which HO-1 expression is inhibited in myeloid cells, including the microglia. INNOVATION: This study suggests the participation of the microglial α7 nAChR in the brain cholinergic anti-inflammatory pathway. CONCLUSION: Activation of the α7 nAChR/Nrf2/HO-1 axis in microglia regulates neuroinflammation and oxidative stress, affording neuroprotection under brain ischemic conditions.

Fully automated multianalyte determination of different classes of pesticides, at picogram per litre levels in water, by on-line solid-phase extraction-liquid chromatography-electrospray-tandem mass spectrometry.

This paper reports the development of a fully automated method for the multianalyte determination of twenty pesticides belonging to different classes (triazines, phenylureas, organophosphates, anilines, acidic, propanil, and molinate) in natural and treated waters. The method, based on on-line solid-phase extraction-liquid chromatography-electrospray-tandem mass spectrometry, is highly sensitive (limits of detection between 0.004 and 2.8 ng L(-1)), precise (relative standard deviations between 2.0 and 12.1%), reliable (two selected reaction-monitoring transitions are monitored per compound), rapid (45 min per sample), and simple. The application of this method to the monitoring of the target compounds in a waterworks revealed the presence of the pesticides investigated at concentrations up to 516 and 82 ng L(-1) (total pesticide concentration) in river water and ground water, respectively, used as sources, and their gradual removal through the purification process.

Multianalyte determination of different classes of pesticides (acidic, triazines, phenyl ureas, anilines, organophosphates, molinate and propanil) by liquid chromatography-electrospray-tandem mass spectrometry.

This work describes the optimization of a liquid chromatography-electrospray-tandem mass spectrometry (LC-ESI-MS-MS) method for the multianalyte determination of twenty pesticides, selected based on current regulations and extent of use. Chromatographic separation was carried out on a Purospher STAR RP-18e column using gradient acetonitrile-water as mobile phase. Triazines, phenylureas, organophosphates, anilines, and molinate were determined in the positive ionization mode, and acidic pesticides and propanil in the negative ion mode. Two different precursor ion-product ion transitions were selected for each analyte and monitored under time scheduled multiple reaction monitoring (MRM) conditions. The optimized method was shown to be linear in the range 1 to 1000 ng/mL with correlation coefficients higher than 0.99 for all but one (diazinon) of the analytes, very sensitive (with limits of detection between 0.010 and 4.528 ng/mL), and repeatable (with relative standard deviations, calculated from the replicate analysis of standard mixtures, lower than 14%). The present work was also devoted to the elucidation of the structures of the principal fragment ions obtained after collision-induced dissociation of the pesticides investigated, an aspect often overlooked in the literature.