TriCurin, a novel formulation of curcumin, epicatechin gallate, and resveratrol, inhibits the tumorigenicity of human papillomaviruspositive head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with about 600,000 new cases diagnosed in the last year. The incidence of human papillomavirus-positive head and neck squamous cell carcinoma (HPV-positive HNSCC) has rapidly increased over the past 30 years prompting the suggestion that an epidemic may be on the horizon. Therefore, there is a clinical need to develop alternate therapeutic strategies to manage the growing number of HPV-positive HNSCC patients. TriCurin is a composition of three food-derived polyphenols in unique stoichiometric proportions consisting of curcumin from the spice turmeric, resveratrol from red grapes, and epicatechin gallate from green tea. Cell viability, clonogenic survival, and tumorsphere formation were inhibited and significant apoptosis was induced by TriCurin in UMSCC47 and UPCI:SCC090 HPV-positive HNSCC cells. Moreover, TriCurin decreased HPV16E6 and HPV16E7 and increased p53 levels. In a pre-clinical animal model of HPV-positive HNSCC, intratumoral injection of TriCurin significantly inhibited tumor growth by 85.5% compared to vehicle group (P \u3c 0.05, n = 7). Our results demonstrate that TriCurin is a potent anti-tumor agent for HPV-positive HNSCC. Further development of TriCurin as a novel anti-cancer therapeutic to manage the HPV-positive HNSCC population is warranted

Rapid evolution of a floral trait following acquisition of novel pollinators

Changes in the pollinator assemblage visiting a plant can have consequences for reproductive success and floral evolution. We studied a recent plant trans‐continental range expansion to test whether the acquisition of new pollinator functional groups can lead to rapid adaptive evolution of flowers. In Digitalis purpurea, we compared flower visitors, floral traits and natural selection between native European populations and those in two Neotropical regions, naturalised after independent introductions. Bumblebees are the main pollinators in native populations while both bumblebees and hummingbirds are important visitors in the new range. We confirmed that the birds are effective pollinators and deposit more pollen grains on stigmas than bumblebees. We found convergent changes in the two new regions towards larger proximal corolla tubes, a floral trait that restricts access to nectar to visitors with long mouthparts. There was a strong positive linear selection for this trait in the introduced populations, particularly on the length of the proximal corolla tube, consistent with the addition of hummingbirds as pollinators. Synthesis. The addition of new pollinators is likely to happen often as humans influence the ranges of plants and pollinators but it is also a common feature in the long‐term evolution of the angiosperms. We show how novel selection followed by very rapid evolutionary change can be an important force behind the extraordinary diversity of flower

A novel curcumin-based vaginal cream Vacurin selectively eliminates apposed human cervical cancer cells

Objective. Human papillomavirus (HPV) infections remain a leading cause of mortality worldwide. In the U.S. strategies via screening and vaccination prevent HPV-associated cervical neoplasms, but consume im- mense healthcare costs. The spice component curcumin has potent anticancer and antiviral properties, which have been difficult to harness as a treatment, due to its poor systemic bioavailability. This project tests the possibility of developing a curcumin-based therapy for cervical cancer. Methods. Using four HPV(+) cervical cancer cell lines and normal fibroblasts we first tested the selectivity and potency of curcumin in eliminating HPV(+) cells. Subsequently, we developed a curcumin-based cervical cream and tested its efficacy in eliminating apposed HPV(+) cells and also its possible side effects on the vaginal epithelium of healthy mice. Results. Curcumin selectively eliminates a variety of HPV(+) cervical cancer cells (HeLa, ME-180, SiHa, and SW756), suppresses the transforming antigen E6, dramatically inhibits the expression of the pro-cancer protein epidermal growth factor receptor (EGFR), and concomitantly induces p53. Additionally, Vacurin, a uniform colloidal solution of curcumin in a clinically used amphipathic vaginal cream, eliminates apposed HeLa cells while suppressing the expression of EGFR. In mice, daily intravaginal application of Vacurin for three weeks produced no change in body weight and when the mice were sacrificed, the vaginal tract epithelium showed no Vacurin-evoked adverse effects. Conclusion. We have developed a curcumin-based vaginal cream, which effectively eradicates HPV(+) cancer cells and does not affect non-cancerous tissue. Our preclinical data support a novel approach for the treatment of cervical HPV infection

State of poeciliid fishes in the international market

Objective: To make a review about the knowledge of the fish of the family poecilidade in Mexico in the main areas of knowledge. Design/methodology/approach: The present review was carried out through the search and bibliographic compilation of literature, as well as in the consultation of articles in different databases, for its subsequent analysis. Results: Poeciliid fish are the most widespread group of ornamental fish internationally, they are found in all international markets, leading productions for aquarium purposes, and therefore have great economic importance within the trade of aquatic organisms for commercial purposes. Ornamental. Limitations on study/implications: The Poeciliids are a well-known group of fish, however information on marketing and specific sales data is limited. Findings/conclusions: The most sold fish is the Guppy (P. reticulata), followed by mollies, platies and swordtails, which constitute the main internationally traded poeciliids.Objetivo: Hacer una revisión y análisis acerca del papel que tienen los peces poecílidos dentro del mercado internacional. Diseño/metodología/aproximación: La presente investigación se realizó mediante la búsqueda y recopilación bibliográfica de literatura, así como en la consulta de artículos en diferentes bases de datos, para su posterior análisis y procesamiento de la información. Resultados: Los peces poecílidos son el grupo de peces ornamentales más extendido a nivel internacional, se encuentran en todos los mercados internacionales, liderando las producciones con fines de acuariofilia, por lo que tienen gran importancia económica dentro del comercio de organismos acuáticos con fines ornamentales Limitaciones del estudio/implicaciones: Los poecílidos son un grupo de peces bien conocido, sin embargo, la información sobre comercialización y datos específicos de venta se encuentra limitado. Hallazgos/conclusiones: El pez más vendido es el Guppy (P. reticulata), seguido de los mollies, platies y colas de espada, los cuales constituyen los principales poecílidos comercializados a nivel internacional

EWOCS-I: The catalog of X-ray sources in Westerlund 1 from the Extended Westerlund 1 and 2 Open Clusters Survey

Context. With a mass exceeding several 104 M⊙ and a rich and dense population of massive stars, supermassive young star clusters represent the most massive star-forming environment that is dominated by the feedback from massive stars and gravitational interactions among stars. Aims. In this paper we present the Extended Westerlund 1 and 2 Open Clusters Survey (EWOCS) project, which aims to investigate the influence of the starburst environment on the formation of stars and planets, and on the evolution of both low and high mass stars. The primary targets of this project are Westerlund 1 and 2, the closest supermassive star clusters to the Sun. Methods. The project is based primarily on recent observations conducted with the Chandra and JWST observatories. Specifically, the Chandra survey of Westerlund 1 consists of 36 new ACIS-I observations, nearly co-pointed, for a total exposure time of 1 Msec. Additionally, we included 8 archival Chandra/ACIS-S observations. This paper presents the resulting catalog of X-ray sources within and around Westerlund 1. Sources were detected by combining various existing methods, and photon extraction and source validation were carried out using the ACIS-Extract software. Results. The EWOCS X-ray catalog comprises 5963 validated sources out of the 9420 initially provided to ACIS-Extract, reaching a photon flux threshold of approximately 2 × 10−8 photons cm−2 s −1 . The X-ray sources exhibit a highly concentrated spatial distribution, with 1075 sources located within the central 1 arcmin. We have successfully detected X-ray emissions from 126 out of the 166 known massive stars of the cluster, and we have collected over 71 000 photons from the magnetar CXO J164710.20-455217.Fil: Guarcello, Mario Giuseppe. Istituto Nazionale di Astrofísica. Osservatorio Astronómico di Palermo; ItaliaFil: Flaccomio, Ettore. Istituto Nazionale di Astrofísica. Osservatorio Astronómico di Palermo; ItaliaFil: Albacete Colombo, Juan Facundo. Universidad Nacional de Río Negro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Almendros Abad, Víctor. Istituto Nazionale di Astrofísica. Osservatorio Astronómico di Palermo; ItaliaFil: Anastasopoulou, Konstantina. Istituto Nazionale di Astrofísica. Osservatorio Astronómico di Palermo; ItaliaFil: Andersen, M.. European Southern Observatory; AlemaniaFil: Argiroffi, C.. Istituto Nazionale di Astrofísica. Osservatorio Astronómico di Palermo; Italia. Università degli Studi di Palermo; ItaliaFil: Bayo, Amelia. European Southern Observatory; AlemaniaFil: Bartlett, E.S.. European Southern Observatory; AlemaniaFil: Bastian, N.. Donostia International Physics Center; España. Basque Foundation For Science; España. Liverpool John Moores University; Reino UnidoFil: De Becker, Michaël. Université de Liège; BélgicaFil: Best, William M. J.. University of Texas at Austin; Estados UnidosFil: Bonito, R.. Istituto Nazionale di Astrofísica. Osservatorio Astronómico di Palermo; ItaliaFil: Borghese, Alice. Instituto de Astrofísica de Canarias; España. Universidad de La Laguna; EspañaFil: Calzetti, D.. University of Massachusetts; Estados UnidosFil: Castellanos, R.. Centro de Astrobiología; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Cecchi Pestellini, C.. Istituto Nazionale di Astrofísica. Osservatorio Astronómico di Palermo; ItaliaFil: Clark, J. S.. The Open University; Reino UnidoFil: Clarke, C. J.. University of Cambridge; Estados UnidosFil: Zelati, Francesco Coti. Instituto de Estudios Espaciales de Cataluña; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Damiani, Jeremy. Istituto Nazionale di Astrofísica. Osservatorio Astronómico di Palermo; ItaliaFil: Drake, J.J.. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Gennaro, Mario. Space Telescope Science Institute; Estados Unidos. University Johns Hopkins; Estados UnidosFil: Mapelli, M.. Università di Padova; Italia. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Martinez Galarza, J. R.. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Micela, G.. Istituto Nazionale di Astrofísica. Osservatorio Astronómico di Palermo; ItaliaFil: Miceli, M.. Istituto Nazionale di Astrofísica. Osservatorio Astronómico di Palermo; Italia. Università degli Studi di Palermo; ItaliaFil: Moraux, E.. Universite Grenoble Alpes; FranciaFil: Winter, A.. Observatoire de la Côte D'azur; Francia. Universite Grenoble Alpes; FranciaFil: Wright, N. J.. Keele University; Reino UnidoFil: Zeidler, Peter. European Southern Observatory; Alemania. Space Telescope Science Institute; Estados Unido

Diagnostic imaging of cervical intraepithelial neoplasia based on hematoxylin and eosin fluorescence

Background Pathological classification of cervical intraepithelial neoplasia (CIN) is problematic as it relies on subjective criteria. We developed an imaging method that uses spectroscopy to assess the fluorescent intensity of cervical biopsies derived directly from hematoxylin and eosin (H&E) stained tissues. Methods Archived H&E slides were identified containing normal cervical tissue, CIN I, and CIN III cases, from a Community Hospital and an Academic Medical Center. Cases were obtained by consensus review of at least 2 senior pathologists. Images from H&E slides were captured first with bright field illumination and then with fluorescent illumination. We used a Zeiss Axio Observer Z1 microscope and an AxioVision 4.6.3-AP1 camera at excitation wavelength of 450–490 nm with emission captured at 515–565 nm. The 32-bit grayscale fluorescence images were used for image analysis. Results We reviewed 108 slides: 46 normal, 33 CIN I and 29 CIN III. Fluorescent intensity increased progressively in normal epithelial tissue as cells matured and advanced from the basal to superficial regions of the epithelium. In CIN I cases this change was less prominent as compared to normal. In high grade CIN lesions, there was a slight or no increase in fluorescent intensity. All groups examined were statistically different. Conclusion Presently, there are no markers to help in classification of CIN I-III lesions. Our imaging method may complement standard H&E pathological review and provide objective criteria to support the CIN diagnosis

Unique synergistic formulation of curcumin, epicatechin gallate and resveratrol, tricurin, suppresses HPV E6, eliminates HPV+ cancer cells, and inhibits tumor progression

Curcumin (from curry) (C) is highly potent against cervical cancer cells (CCC), but poor bioavailability has limited its clinical use. Similar natural polyphenols resveratrol (from grapes) (R), and epicatechin gallate (from green tea) (E) also display activity against CCC. By treating CCC (HeLa) with C, E, or R, or combinations of these compounds, we computed combination indices and observed a strong synergism among C, E, and R at the unique molar ratio 4:1:12.5. This combination, named as TriCurin, rapidly down regulated HPV18 E6 and NF-kB expression while concomitantly inducing the tumor suppressor protein p53 in HeLa cells. In the mouse c-Ha-ras and HPV16 E6, E7-expressing TC-1 CCC, both C and TriCurin elicited suppression of E6, induction of both p53 and acetyl-p53 (activated p53), and activation of caspase-3, but the TriCurinevoked changes were several-fold greater than that produced by curcumin (4.7-fold for E6 inhibition, and 2-fold, 6-fold, and 1.7-fold for the induction of p53, acetyl-p53, and active caspase-3, respectively). Consequently, TriCurin was more potent in killing TC-1 and HeLa cells. Intralesional TriCurin treatment of tumors generated in mice by subcutaneously implanting the TC-1 CCC caused an 80–90% decrease in tumor growth. The ability of C to eliminate HeLa cells was significantly stabilized when delivered as TriCurin than when delivered alone. Topical application of TriCurin dispersed in a cream base afforded efficient transfer of C across the skin. Subcutaneous TriCurin injection yielded no adverse effect in tumor-naïve healthy mice. Thus, TriCurin is a safe and promising therapeutic agent against HPV-associated disease

Commissioning Plan of the IFMIF-DONES Accelerator

IFMIF-DONES (International Fusion Materials Irradiation Facility- DEMO-Oriented Neutron Early Source) - a powerful neutron irradiation facility for studies and certification of materials to be used in fusion reactors - is planned as part of the European roadmap to fusion electricity. Its main goal will be to characterize and to qualify materials under irradiation in a neutron field similar to the one faced in a fusion reactor. The intense neutron source is produced by impinging deuterons, from high-power linear deuteron accelerator, on a liquid lithium curtain. The facility has accomplished the preliminary design phase and is currently in its detailed design phase. At the present stage, it is important to have a clear understanding of how the commissioning of the facility will be performed, especially the commissioning of a 5 MW CW deuteron beam, together with the lithium curtain and the beam optimization for the neutron irradiation. In this contribution, the present plans for the hardware and beam commissioning of the accelerator will be given, focusing on the most critical aspects of the tiered approach and on the integration of the procedure with the lithium and tests systems

Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity

<p>Abstract</p> <p>Background</p> <p>Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of gluten. Gluten-sensitive individuals (GS) cannot tolerate gluten and may develop gastrointestinal symptoms similar to those in CD, but the overall clinical picture is generally less severe and is not accompanied by the concurrence of tissue transglutaminase autoantibodies or autoimmune comorbidities. By studying and comparing mucosal expression of genes associated with intestinal barrier function, as well as innate and adaptive immunity in CD compared with GS, we sought to better understand the similarities and differences between these two gluten-associated disorders.</p> <p>Methods</p> <p>CD, GS and healthy, gluten-tolerant individuals were enrolled in this study. Intestinal permeability was evaluated using a lactulose and mannitol probe, and mucosal biopsy specimens were collected to study the expression of genes involved in barrier function and immunity.</p> <p>Results</p> <p>Unlike CD, GS is not associated with increased intestinal permeability. In fact, this was significantly reduced in GS compared with controls (<it>P </it>= 0.0308), paralleled by significantly increased expression of claudin (CLDN) 4 (<it>P </it>= 0.0286). Relative to controls, adaptive immunity markers interleukin (IL)-6 (<it>P </it>= 0.0124) and IL-21 (<it>P </it>= 0.0572) were expressed at higher levels in CD but not in GS, while expression of the innate immunity marker Toll-like receptor (TLR) 2 was increased in GS but not in CD (<it>P </it>= 0.0295). Finally, expression of the T-regulatory cell marker FOXP3 was significantly reduced in GS relative to controls (<it>P </it>= 0.0325) and CD patients (<it>P </it>= 0.0293).</p> <p>Conclusions</p> <p>This study shows that the two gluten-associated disorders, CD and GS, are different clinical entities, and it contributes to the characterization of GS as a condition associated with prevalent gluten-induced activation of innate, rather than adaptive, immune responses in the absence of detectable changes in mucosal barrier function.</p