A role for antizyme inhibitor in cell proliferation

Acknowledgments We thank Ewa Dahlberg and Lena Thiman for expert technical help with cell culturing and HPLC, respectively. The authors acknowledge financial support from the Portuguese Foundation for Science and Technology—SFRH/BD/46364/2008 (PhD fellowship to T. M. S.), the Gunnar Nilssons Cancer Foundation, the Mrs Berta Kamprad Foundation and the Per-Eric and Ulla Schyberg Foundation. Heather Wallace was supported by a visiting scholarship from Lund University. We are grateful for the generous supply of AzI antibody and pcDNA3.1-AzI from Dr. Senya Matsufuji and Dr. Yasuku Murakami (Tokyo, Japan), and Dr. Leif Andersson (Helsinki, Finland), respectively.Peer reviewedPublisher PD

Oncogenic Gain of Function in Glioblastoma Is Linked to Mutant p53 Amyloid Oligomers.

Tumor-associated p53 mutations endow cells with malignant phenotypes, including chemoresistance. Amyloid-like oligomers of mutant p53 transform this tumor suppressor into an oncogene. However, the composition and distribution of mutant p53 oligomers are unknown and the mechanism involved in the conversion is sparse. Here, we report accumulation of a p53 mutant within amyloid-like p53 oligomers in glioblastoma-derived cells presenting a chemoresistant gain-of-function phenotype. Statistical analysis from fluorescence fluctuation spectroscopy, pressure-induced measurements, and thioflavin T kinetics demonstrates the distribution of oligomers larger than the active tetrameric form of p53 in the nuclei of living cells and the destabilization of native-drifted p53 species that become amyloid. Collectively, these results provide insights into the role of amyloid-like mutant p53 oligomers in the chemoresistance phenotype of malignant and invasive brain tumors and shed light on therapeutic options to avert cancer

Aleurites moluccana (L.) Willd. Leaves: Mechanical Antinociceptive Properties of a Standardized Dried Extract and Its Chemical Markers

Seeking to develop a new analgesic phytomedicine, a spray-dried extract (SDE) of Aleurites moluccana (L.) Willd. leaves was developed in scale up (5 kg). The SDE was standardized at 3% w/w in relation to the flavonoid 2′′-O-rhamnosylswertisin. The SDE batches were evaluated in relation to their physical, physiochemical, and pharmacological characteristics. The results demonstrated the reproducibility of the scale up SDE process which, when dosed orally, reduced carrageenan-induced mechanical hypernociception, with an ID50% of 443 mg/kg. Similar results were obtained with animals injected with complete Freund's adjuvant (CFA), in which SDE caused inhibition of 48 ± 4%. SDE was effective in preventing prostaglandin E2 (PGE2)-induced mechanical hypernociception (inhibition of 26 ± 10% and 33 ± 3%, at 250 and 500 mg/kg, respectively). Swertisin and 2′′-O-rhamnosylswertisin isolated from the own extract were effective in inhibiting the hypernociceptive response induced by carrageenan (70 ± 2% and 50 ± 5%, resp.). Furthermore, 2′′-O-rhamnosylswertisin was capable of significantly inhibiting the mechanical sensitization induced by CFA or PGE2, with inhibitions of 25 ± 3% and 94 ± 6%, respectively. These results suggest that the effects of SDE are related, at least in part, to the presence of these flavonoids

Prevalence and Characteristics of the O122 Pathogenicity Island in Typical and Atypical Enteropathogenic Escherichia coli Strains

The presence of the pathogenicity island (PAI) O122 genes, efa1 (lifA), sen, pagC, nleB, and nleE, in typical and atypical enteropathogenic Escherichia coli (EPEC) strains was investigated. the simultaneous occurrence of all genes was statistically associated with diarrhea due to atypical EPEC. Detection of the complete PAI O122 could aid in the identification of potential pathogenic strains of atypical EPEC.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Microbiol, São Paulo, BrazilSecao Bacteriol Inst Adolfo Lutz, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol, São Paulo, BrazilFAPESP: 08/53812-4Web of Scienc

Systematic Review and Critical Analysis of Cost Studies Associated with Parkinson's Disease

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease worldwide, affecting more than four million people. Typically, it affects individuals above 45, when they are still productive, compromising both aging and quality of life. Therefore, the cost of the disease must be identified, so that the use of resources can be rational and efficient. Additionally, in Brazil, there is a lack of research on the costs of neurodegenerative diseases, such as PD, a gap addressed in this study. This systematic review critically addresses the various methodologies used in original research around the world in the last decade on the subject, showing that costs are hardly comparable. Nonetheless, the economic and social impacts are implicit, and important information for public health agents is provided.Hosp Israelita Albert Einstein, Programa Posgrad, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Movement Disorders Dept Neurol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Sao Paulo, SP, BrazilHosp Israelita Albert Einstein, Neurol Program, Sao Paulo, SP, BrazilMovement Disorders Department in Neurology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, BrazilUniversidade Federal de São Paulo (UNIFESP), São Paulo, SP, BrazilWeb of Scienc

Chemical composition, antibacterial and antioxidant activities of the essential oil from Vismia guianensis fruits

In recent decades, the essential oils of plants have drawn great interest as sources of natural products. Essential oil from the fruits of Vismia guianensis was tested for its chemical constituents and antimicrobial and antioxidant activities. Gas chromatography/mass spectrometry (GC-MS) analysis of the essential oil revealed the presence of 38 sesquiterpenoids. The major components were β-caryophyllene (25.8%), α-copaene (13.1%), and δ-cadinene (11.6%). Antimicrobial activities were measured against six species of Gram negative and seven species of Gram positive bacteria and showed antibacterial activity against the human pathogenic Gram-positive bacteria Staphylococcus lentus with minimum inhibitory concentration (MIC) values of 78 μg/ml. The antioxidant activity of the essential oil was evaluated using the beta carotene/linoleic acid assay and showed antioxidant activity.Key words: Vismia guianensis, chemical composition, antibacterial, antioxidant, fruits, essential oil

Assay of total flavonoids in dried extract of Aleurites moluccana

The flavonoid 2''-O-rhamnosylswertisin in Aleurites moluccana is related to the therapeutic effect of the plant, making it an adequate marker. In this work a method of total flavonoid assay was developed and validated, expressed in its marker. A double reflux of dried extract obtained from A. moluccana leaves (0.4 g) with 50 % (v/v) ethanol was carried out. After filtration, the solution was complexed with 2 % AlCl3 in 50 % (v/v) ethanol, and the absorbance read at 397 nm after 90 min. The number of refluxes (1-2), volume of complexing agent (0.5-3 mL), stability of complexing agent and complexation time (15-120 min) were evaluated. The specific absorption coefficient (E1%1cm) of the marker compound was 77.18. The method showed linearity (r2 > 0.99) at the tested range, good precision (RSD % ≈ 5 %, intra-day and inter-days) and accuracy of 99.3 %. The dried extract of leaves of A. moluccana showed 0.15 % total flavonoids, expressed in 2''-O-rhamnosylswertisin.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Biochemical and histopathological impacts of rutile and anatase (TiO2 forms) in Mytilus galloprovincialis

Titanium dioxide (TiO2) particles have been widely used in various industrial applications and consumer products. Due to their large production and use, they will eventually enter into aquatic environments. Once in the aquatic environment TiO2 particles may interact with the organisms and induce toxic effects. Since the most common crystallographic forms of TiO2 are rutile and anatase, the present study evaluated the effect of these two forms of TiO2 particles in Mytilus galloprovincialis. For this, mussels were exposed to different concentrations of rutile and anatase particles (0, 5, 50, 100 µg/L) for twenty-eight days. Ti concentrations, histopathological alterations and biochemical effects were evaluated. Similar Ti concentrations were found in mussels exposed to rutile and anatase, with the highest values in mussels exposed to the highest exposure concentration. Histopathological results demonstrated that both forms of TiO2 induced alterations on gills and digestive glands along the increasing exposure gradient. Biochemical markers showed that mussels exposed to rutile maintained their metabolic capacity (assessed by the activity of the Electron Transport System, ETS), while anatase increased the metabolism of mussels. Mussels exposed to rutile increased their detoxifying defences which, due to the low tested concentrations, were sufficient to avoid cellular damage. On the other hand, mussels exposed to anatase suffered cellular damages despite the increase of the antioxidant defences which may be related to the high ETS activity. Both rutile and anatase particles were toxic to M. galloprovincialis, being the highest oxidative stress exerted by the crystalline form anatase.publishe

Thermal, mechanical and chemical analysis of poly(vinyl alcohol) multifilament and braided yarns

Poly(vinyl alcohol) (PVA) in multifilament and braided yarns (BY) forms presents great potential for the design of numerous applications. However, such solutions fail to accomplish their requirements if the chemical and thermomechanical behaviour is not sufficiently known. Hence, a comprehensive characterisation of PVA multifilament and three BY architectures (6, 8, and 10 yarns) was performed involving the application of several techniques to evaluate the morphological, chem- ical, thermal, and mechanical features of those structures. Scanning electron microscopy (SEM) was used to reveal structural and morphological information. Differential thermal analysis (DTA) pointed out the glass transition temperature of PVA at 76 °C and the corresponding crystalline melt- ing point at 210 °C. PVA BY exhibited higher tensile strength under monotonic quasi-static loading in comparison to their multifilament forms. Creep tests demonstrated that 6BY structures present the most deformable behaviour, while 8BY structures are the least deformable. Relaxation tests showed that 8BY architecture presents a more expressive variation of tensile stress, while 10BY of- fered the least. Dynamic mechanical analysis (DMA) revealed storage and loss moduli curves with similar transition peaks for the tested structures, except for the 10BY. Storage modulus is always four to six times higher than the loss modulus.This work was funded by European Regional Development funds (FEDER) through the Competitiveness and Internationalization Operational Program (POCI)—COMPETE andby Na-tional Funds through Portuguese Fundação para a Ciência e Tecnologia (FCT) under the project UID/EMS/50022/2020, UID/EEA/04436/2019 andUID/ CTM/00264/2019. Andrea Zille acknowledges financial support of the FCT through the project PTDC/CTM-TEX/28295/2017,and Nuno Dourado acknowledges financial support of the FCT through the project PTDC/EME-SIS/28225/2017. M.F.S.M. de Moura acknowledges the ‘Laboratório Associado de Energia, Transportes e Aeronáutica’ (LAETA) for the financial support

Highly conducting bombyx mori silk fibroin-based electrolytes incorporating glycerol, dimethyl sulfoxide and [Bmim]PF6

Green, transparent and flexible electrolyte films composed of a Bombyx mori silk fibroin (SF) host biopolymer doped with glycerol (G), dimethyl sulfoxide (DMSO, D) and 1-butyl-3-methylimidazolium hexafluorophosphate ([Bmim]PF6) ionic liquid (IL), were synthesized. The materials were represented by the notation SF@GD@ILx (x = 15, 20 and 30 is the mass ratio of SF/[Bmim]PF6 in %). SF@, SF@G, SF@D and SF@GD samples were also prepared. DMSO was found to play a dual-role, acting as solvent of [Bmim]PF6, and enhancing ionic conductivity. DMSO, alone or combined with [Bmim]PF6, led to the increase of the mean roughness and induced the formation of more ordered Silk II conformations (beta-sheets). No structural modifications were detected in the SF@GD@ILx samples upon increasing the temperature up to 100 degrees C. The highest ionic conductivity was exhibited by the IL-rich sample SF@GD@IL30 (1.07 and 4.61 mS cm(-1), at 22 and 100 degrees C, respectively). In the [Bmim]PF6-doped electrolytes "free" and coordinated PF6- ions coexist. The weight losses occurring below 200 degrees C involved essentially the release of adsorbed water and DMSO. The suitable mechanical properties, high ionic conductivity and good electrochemical stability suggest that these electrolytes are attractive candidates for application in electrochemical devices.Veronica de Zea Bermudez would like to express her gratitude to Professor Michel Armand who, during her PhD thesis at Grenoble (1989-1992), was an endless source of ideas that made her work productive and stimulating. His qualities, as an inspiring and extraordinary scientist, equal his kindness, generosity and great heart. This work was supported by National funds by Foundation for Science and Technology (FCT) in the framework of the Strategic Funding UID/QUI/00686/2018, UID/QUI/00686/2019, UID/QUI/50006/2019 and UID/QUI/00313/2020. The authors thank FEDER funds through the COMPETE 2020 Program and National Funds through FCT under the projects PEst-OE/QUI/UI0616/2014, LUMECD (POCI-01-0145-FEDER-016884 and PTDC/CTMNAN/0956/2014), UniRCell (POCI-01-0145-FEDER-016422 and SAICTPAC/0032/2015), PORPLANTSURF (POCI-01-0145FEDER-029785 and PTDC/CTM-REF/29785/2017), and NORTE01-0145-FEDER-030858. R.F.P.P thanks FCT-UM for the researcher contract in the scope of Decreto-Lei 57/2016 and 57/2017. H.M.R. Goncalves was funded by PTDC/BTM-MAT/30858/2017