Low expression of estrogen receptor β in T lymphocytes and high serum levels of anti-estrogen receptor α antibodies impact disease activity in female patients with systemic lupus erythematosus

BACKGROUND: Current evidence indicates that estrogens, in particular 17β-estradiol (E2), play a crucial role in the gender bias of autoimmune diseases although the underlying molecular mechanisms have not yet been fully elucidated. Immune cells have estrogen receptors (ERs), i.e., ERα and ERβ, that play pro- and anti-inflammatory functions, respectively, and the presence of one estrogen receptor (ER) subtype over the other might change estrogen effects, promoting or dampening inflammation. In this study, we contributed to define the influences of E2 on T cells from female patients with systemic lupus erythematosus (SLE), a representative autoimmune disease characterized by a higher prevalence in women than in men (female/male ratio 9:1). Particularly, our aim was to evaluate whether alterations of ERα and ERβ expression in T cells from female SLE patients may impact lymphocyte sensitivity to E2 and anti-ERα antibody (anti-ERα Ab) stimulation interfering with cell signaling and display a direct clinical effect. METHODS: Sixty-one premenopausal female patients with SLE and 40 age-matched healthy donors were recruited. Patients were divided into two groups based on the SLE Disease Activity Index 2000 (SLEDAI-2K) (i.e., <6 and ≥6). ER expression was evaluated in T lymphocytes by flow cytometry, immunofluorescence, and Western blot analyses. Serum anti-ERα Ab levels were analyzed by enzyme-linked immunosorbent assay (ELISA). ER-dependent signaling pathways were measured by a phosphoprotein detection kit. RESULTS: Intracellular ERβ expression was significantly lower in T cells from patients with SLEDAI-2K ≥6 as compared with healthy donors and patients with SLEDAI-2K <6 and negatively correlated with disease activity. The expression of intracellular and membrane-associated-ERα was similar in SLE and control T cells. ER-dependent signaling pathways were activated in T cells from SLE patients with SLEDAI-2K ≥6, but not with SLEDAI-2K <6, when both membrane and intracellular ERs were stimulated by co-treatment with E2 and anti-ERα Abs. CONCLUSIONS: Our results demonstrate an altered ER profile in SLE patients, possibly contributing to SLE pathogenesis and interfering with clinical activity, and highlight the potential exploitation of T cell-associated ERβ as a biomarker of disease activity

Cathepsin B inhibition interferes with metastatic potential of human melanoma: an in vitro and in vivo study

<p>Abstract</p> <p>Background</p> <p>Cathepsins represent a group of proteases involved in determining the metastatic potential of cancer cells. Among these are cysteinyl- (e.g. cathepsin B and cathepsin L) and aspartyl-proteases (e.g. cathepsin D), normally present inside the lysosomes as inactive proenzymes. Once released in the extracellular space, cathepsins contribute to metastatic potential by facilitating cell migration and invasiveness.</p> <p>Results</p> <p>In the present work we first evaluated, by <it>in vitro </it>procedures, the role of cathepsins B, L and D, in the remodeling, spreading and invasiveness of eight different cell lines: four primary and four metastatic melanoma cell lines. Among these, we considered two cell lines derived from a primary cutaneous melanoma and from a supraclavicular lymph node metastasis of the same patient. To this purpose, the effects of specific chemical inhibitors of these proteases, i.e. CA-074 and CA-074Me for cathepsin B, Cathepsin inhibitor II for cathepsin L, and Pepstatin A for cathepsin D, were evaluated. In addition, we also analyzed the effects of the biological inhibitors of these cathepsins, i.e. specific antibodies, on cell invasiveness. We found that i) cathepsin B, but not cathepsins L and D, was highly expressed at the surface of metastatic but not of primary melanoma cell lines and that ii) CA-074, or specific antibodies to cathepsin B, hindered metastatic cell spreading and dissemination, whereas neither chemical nor biological inhibitors of cathepsins D and L had significant effects. Accordingly, <it>in vivo </it>studies, i.e. in murine xenografts, demonstrated that CA-074 significantly reduced human melanoma growth and the number of artificial lung metastases.</p> <p>Conclusions</p> <p>These results suggest a reappraisal of the use of cathepsin B inhibitors (either chemical or biological) as innovative strategy in the management of metastatic melanoma disease.</p

Patrimonialization process of an 18th century cannon from San Antonio de Areco, Province of Buenos Aires

En este trabajo se presenta el desarrollo del proceso de patrimonialización de un cañón de hierro fabricado en 1789, probablemente en una fundición sueca. La pieza de artillería fue recuperada a comienzos del siglo XX del solar en donde funcionó el antiguo Juzgado de Paz y la Comisaría de San Antonio de Areco. Dicha pieza, forma parte de un conjunto de armas de fuego vinculado a la defensa del territorio en tiempos históricos del cual participaron milicianos locales.En 1927 el cañón fue donado al Museo Colonial e Histórico de Luján y años más tarde transferido al Museo Gauchesco Ricardo Güiraldes. El proceso de patrimonialización para su puesta en valor fue iniciado junto a personal del museo y al Programa de Protección y Rehabilitación del patrimonio Urbano y Rural del Municipio de Areco, a través de un trabajo colaborativo de Ciencia Participativa en el marco del proyecto ArqueoLab-UBA. Este proceso permitió visibilizar la historia de vida del cañón y difundir las buenas prácticas de protección del patrimonio cultural mediante estrategias de investigación, conservación y de difusión concretas y vivenciales, y de este modo fomentar la incorporación de los hechos históricos locales en la memoria social de la comunidad y generar conciencia sobre el acervo cultural local.This work presents the patrimonialization process of an iron cannon manufactured in 1789, most likely in a Swedish foundry. This gun was recovered from the site where the former Justice of the Peace Court and the local Commissioner functioned at the beginning of the 20th century. This piece belongs to a set of weapons linked to the defense of the territory conducted by local militiamen in historical times. In 1927 the cannon was donated to the Colonial and Historical Museum of Lujan for exhibition and it was transferred to the Ricardo Güiraldes Gaucho Museum years later. The patrimonialization process was developed by the Municipal Urban and Rural Heritage Protection and Rehabilitation Program, through a collaborative work of Participatory Science framed in an ArqueoLab-UBA project. This process allowed making visible the cannon life history and stimulate good practices for the protection of cultural heritage through concrete and experiential research, conservation and dissemination strategies, which in turn promoted the incorporation of local historical events into the community's social memory and raised awareness about local cultural heritage.Fil: Acevedo, Verónica Judith. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Arqueología; ArgentinaFil: Staropoli, Laura. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Arqueología; ArgentinaFil: Herrera, Valeria. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Arqueología; ArgentinaFil: Avido, Daniela Noemi. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Arqueología; ArgentinaFil: Vitores Spinetta, Marcelo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Arqueología; ArgentinaFil: Soto, Daiana Marilé. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Arqueología; ArgentinaFil: Landa, Carlos Gilberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Arqueología; ArgentinaFil: Ciarlo, Nicolás Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Arqueología; ArgentinaFil: Gómez Coronado, Micaela. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Arqueología; ArgentinaFil: del Savio, Priscila Ailen. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Arqueología; Argentin

Research procedures for Vuelta de Obligado site, San Pedro, province of Buenos Aires

En noviembre de 1845 en Vuelta de Obligado se produce un enfrentamiento terrestre-naval entre fuerzas de la Confederación Argentina y una flota anglo-francesa. Los objetos y estructuras que quedaron como consecuencia del evento, más la posterior influencia de procesos de transformación, dejaron como resultado un sitio arqueológico con varios palimpsestos y recurrentemente saqueado; así la mayoría de los hallazgos son fragmentos y no piezas enteras, ya extraídas por huaqueros. Hasta la fecha excavamos más de 300 m² en distintas áreas, priorizando los “núcleos de la batalla”, aquellos lugares usados con mayor intensidad que dejaron una mayor densidad de restos; recuperamos materiales en transectas ubicadas en playas del río Paraná y realizamos sondeos y prospecciones. El registro arqueológico presenta conjuntos de vidrio, metal, loza, madera, huellas de postes, etc. Aquí exponemos la estrategia respecto del trabajo de campo, gabinete y damos a conocer los resultados luego de más de veinte campañas desarrolladas.Em novembro de 1845 em Volta de Obrigado produzse um confronto terrestrenaval entre forças da Confederação Argentina e uma frota anglo-francesa. Os objetos e estruturas que ficaram como consequência do evento, mais a posterior influência de processos de transformação, deixaram como resultado um lugar arqueológico com vários palimpsestos e recurrentemente saqueado; assim a maioria dos achados são fragmentos e não peças inteiras, já extraídas por huaqueros. Até a data escavamos mais de 300 m² em diferentes áreas, priorizando os “núcleos da batalha”, aqueles lugares usados com maior intensidade que deixaram uma maior densidade de restos; recuperamos materiais em transectas localizadas em praias do rio Paraná e realizamos sondagens e prospecciones. O registro arqueológico apresenta conjuntos de vidro, metal, loza, madeira, impressões de mastros, etc. Aqui expomos a estratégia respeito do trabalho de campo, gabinete e damos a conhecer os resultados depois a mais de vinte campanhas desenvolvidas.In November 1845, a naval and terrestrial battle between the forces of the Argentinean Confederation and an Anglo-French fleet took place in Vuelta de Obligado, Province of Buenos Aires. The objects and structures which survived after this event, together with the ulterior influence of the formation processes, resulted in an archaeological site characterized by palimpsests. Moreover, this location was under the effects of several looters. Thus, most of the materials located during the archaeological works are fragmented. Up to this date, more than 300 m2 were excavated. The research was performed in different areas of the site, emphasizing the “cores of the battle”, those places used more intensively and where a major density of remains were fund. Archaeological surveys and test pits, as well as recovery of materials, were conducted along the Parana River coast. The archaeological record includes a wide variety of artifacts of glass, metal, ceramic and wood, and post traces carved in the tosca-rock, among others. In this paper, the fieldwork and cabinet research strategy employed in Vuelta de Obligado are discussed. Besides, the results obtained after fifteen years and more than twenty campaigns in this site are presented.Fil: Ramos, Mariano Sergio. Universidad Nacional de Luján; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lanza, Matilde Mabel. Universidad Nacional de Luján; ArgentinaFil: Raies, Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Luján. Departamento de Ciencias Sociales; ArgentinaFil: Helfer, Veronica Lucia. Universidad Nacional de Luján; ArgentinaFil: Bognanni, Fabián Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Lanús; Argentina. Universidad Nacional de Luján; ArgentinaFil: Salerno, Virginia Mariana. Universidad Nacional de Luján; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Leiva, Carolina. Universidad Nacional de Luján; ArgentinaFil: Ciarlo, Nicolás Carlos. Universidad Nacional de Luján; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Darigo, Mariano Héctor. Universidad Nacional de Rosario. Facultad de Humanidades y Artes; ArgentinaFil: Warr, Matias Luciano. Universidad Nacional de Rosario. Facultad de Humanidades y Artes; ArgentinaFil: Dottori, Carolina. Universidad Nacional de Rosario. Facultad de Humanidades y Artes; ArgentinaFil: Alanís, Sandra. Universidad Nacional de Luján; ArgentinaFil: Umaño Bertola, Milva Ximena. Universidad Nacional de Luján; ArgentinaFil: Pugliese, Agustina Soledad. Universidad Nacional de Luján; ArgentinaFil: Presas, Sebastián. Universidad Nacional de Luján; ArgentinaFil: López, Ariel. Universidad Tecnológica Nacional; ArgentinaFil: Sportelli, Paola. Universidad Nacional de Rosario. Facultad de Humanidades y Artes; ArgentinaFil: Gómez, Daniel. Universidad Nacional de Luján; ArgentinaFil: Gómez, Marcelo. Universidad Nacional de Luján; ArgentinaFil: Raño, Julia. Universidad Nacional de Luján; ArgentinaFil: Santo, Carolina. Universidad Nacional de Luján; ArgentinaFil: Milani, María Laura Luciana. Universidad Nacional de Luján; ArgentinaFil: Pousa, Yesica. Universidad Nacional de Luján; ArgentinaFil: Lopez, Augusto. Universidad Nacional de Luján; ArgentinaFil: Rodríguez, Rocío. Universidad Nacional de Luján; ArgentinaFil: Rodríguez, Lucía. Universidad Nacional de Luján; Argentin

HELMINTH OF LEPUS EUROPAEUS: PARASITE ECOLOGY IN A DECLINING POPULATION

Since the Seventies, a reduction of the European brown hare population (Lepus europaeus) has been observed in most European Countries, including Italy. This reduction suddenly accelerated, at least in some italian areas areas, from 2008 and is still continuing. The studied hares come from the eastern hunting-management district of the Province of Bologna (Emilia-Romagna Region) known as ATCBO2. In ATCBO2, both the hares hunted in the hunting areas and the hares captured in the protected areas severely dropped from 2008-09. For example, about six thousands hares were hunted in 2009-10 while about four thousands were hunted in 2015-16; consistently, captured hares were more than 2 thousands in 2008-09 and about seven hundred in 2015-16. However, the same data suggest a reduced speed of hare decline from 2013-14, when the hare population seems to stabilize at low densities. 54 and 61 hares legally hunted in 2013-14 and 2015-16 hunting season, respectively, were examinded for helminth parasites. Sex and full weight was recordered by hunters; age was estimated observing Stroh\u2019s tubercle. No significant difference in the sampled hare population was found between the two hunting seasons: sex-ratio, age-ratio and full weigh was similar in both years. In both hunting seasons, the intestinal nematode Trichostrongylus retortaeformis and the visceral larval form of the tapeworm Taenia pisiformis (cysticercus) were collected; moreover, lesions ascribed to lung nematode infection were observed in 3+3 hares collected in each hunting season. In the second hunting season only, the nematode Trichuris sp. and the filarial nematode Micipsella numidica were also collected from the intestine and the sierosae, respectively. Parasite biodiversity was, therefore, particularly low in both seasons, but improved in the second one. Significant differences between the two hunting seasons were observed for both T. pisiformis and T. retortaeformis. T. pisiformis infection was less frequent in 2015-16 (3.28%) than in 2013-14 (14.81%); on the contrary, T. retortaeformis abundance was significantly higher in the second hunting season. While T. pisiformis abundance appeared to be negatively related with the weight of the hares in the first hunting season, T. retortaeformis abundance was higher in heavier hosts in both seasons. Both parasites are typical of adult hosts: T. retortaeformis was significantly more abundant in adults and T. pisiformis cysticerci were never isolated in animals younger than 7 month. From 2007-08 hunters (and mass-media) reported a sudden increase of hares infected by T.pisiformis cysticerci, seldom or even never found before in the same area. Previous reports about hare parasites showed quite composite helminth communities, with different helmith species parasitising the gastro-intestinal tract of the hares. The results of the present study reveal an atypical parasite situation, with the strong dominance of one gastro-intestinal helminth species only and the appearance of heavy infections due to cysticerci of T. pisiformis. The difference in parasite infections suggest a modification of the host-parasite relationship over time. The hares examined in the first hunting season show a very critical parasite situation, with T. pisiformis possibly affecting host condition and a strongly depauperated intestinal helminth community dominated by T. retortaeformis alone. The reduction of T. pisiformis infection two years later and the appearance of other helminth species suggest improved host-parasite relationship and could indicate that the period of hare population decline is going to end up. It is impossible to know if parasites played any role in promoting hare population decline, but it is very difficult that T. pisiformis alone could have induced such a dramatic host decline. Hosts and parasites appears, rather, to be tied by a common ecological destiny

El Ángel: Un accidente naval en Banco Chinchorro

Derivado de la elaboración de la carta arqueológica de la Reserva de la Biosfera Banco Chinchorro, Quintana Roo, integrada por la Subdirección de Arqueología Subacuática del INAH desde el 2006 con el apoyo de pescadores y de la Comisión Nacional de Áreas Naturales Protegidas, se cuenta con el registro de 69 contextos conformados por naufragios y restos arqueológicos asociados con la tecnología náutica de los siglos XVI al XXI. Entre los naufragios destaca el pecio El Ángel dadas sus características constructivas, el cargamento que transportaba y sus condiciones de preservación. En este artículo se exponen los avances de las investigaciones arqueológicas en este pecio, que han aportado información sobre los cambios en la construcción naval y el comercio del codiciado palo de tinte o de Campeche durante la primera mitad del siglo XIX.Fil: Marín Carrillo, Laura Inés. Instituto Nacional de Antropología e Historia; MéxicoFil: Ciarlo, Nicolás Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Arqueología; ArgentinaFil: Zuccolotto, Andrés. Colegio de Michoacán; Méxic

Ammonium Glycyrrhizinate Prevents Apoptosis and Mitochondrial Dysfunction Induced by High Glucose in SH-SY5Y Cell Line and Counteracts Neuropathic Pain in Streptozotocin-Induced Diabetic Mice

Glycyrrhiza glabra, commonly known as liquorice, contains several bioactive compounds such as flavonoids, sterols, triterpene, and saponins; among which, glycyrrhizic acid, an oleanane-type saponin, is the most abundant component in liquorice root. Diabetic peripheral neuropathy is one of the major complications of diabetes mellitus, leading to painful condition as neuropathic pain. The pathogenetic mechanism of diabetic peripheral neuropathy is very complex, and its understanding could lead to a more suitable therapeutic strategy. In this work, we analyzed the effects of ammonium glycyrrhizinate, a derivate salt of glycyrrhizic acid, on an in vitro system, neuroblastoma cells line SH-SY5Y, and we observed that ammonium glycyrrhizinate was able to prevent cytotoxic effect and mitochondrial fragmentation after high-glucose administration. In an in vivo experiment, we found that a short-repeated treatment with ammonium glycyrrhizinate was able to attenuate neuropathic hyperalgesia in streptozotocin-induced diabetic mice. In conclusion, our results showed that ammonium glycyrrhizinate could ameliorate diabetic peripheral neuropathy, counteracting both in vitro and in vivo effects induced by high glucose, and might represent a complementary medicine for the clinical management of diabetic peripheral neuropathy

Curcumin-loaded Poly (d,l-lactide-co-glycolide) nanovesicles induce antinociceptive effects after local administration in mice

Both acute and chronic pain are the most widespread medical issue strongly affecting people in terms of health and quality of life. Unlike acute pain, chronic pain is a pathophysiological state arising from the alteration of the peripheral and/or central nervous systems. It is frequently accompanied by the onset of hyperalgesia (increased sensitivity to pain) and allodynia (painful sensation in response to usually innocuous stimuli). Pain is currently treated with two major groups of analgesic drugs, namely non-steroidal anti-inflammatory drugs (NSAIDs) and opioids; their use is associated with important side effects, which include gastrointestinal lesions [1] and nephrotoxicity [2]; in the case of NSAIDs, respiratory depression, tolerance and physical dependence for opioids [3]. For this reason, there is growing interest for the identification of alternative therapeutic strategies. Curcumin (1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a yellow polyphenol, diferuloylmethane, extracted from the rhizomes of turmeric (Curcuma longa)[4]. The therapeutic properties of curcumin are well known indeed possesses low intrinsic toxicity along with a wide range of pharmacological activities that include antitumor, anti-amyloid, antioxidant and anti-inflammatory capacities [5]. Antinociceptive properties of curcumin have also been reported in preclinical studies [6], but its poor bioavaibility limits clinical use as analgesic. Polymeric nanoparticle-based drug delivery is being increasingly investigated as a delivery route able to overcome many obstacles associated with the delivery of free drugs. Recently, we investigated the effects of curcumin-loaded PLGA nanovesicles (PLGA-CUR) administered via intravenous (i.v.) or intrathecal (i.t.) routes in several experimental models of pain [7]. We found that i.v. or i.t. routes of administration of PLGA-CUR nanoformulations were effective in reducing the nociception induced by chemical stimuli or after the ligation of the sciatic nerve in mice [7]. In the present study, putative antinociceptive effects induced by CUR and PLGA-CUR after local subcutaneous administration was investigated in two animal models of pain i.e. the formalin test and the hyperalgesia induced by zymosan. We found PLGA-CUR vesicles able to reduce nociception induced by chemical stimuli, whereas CUR alone induced only a transient but not significant antinociceptive effects. These results obtained after acute subcutaneous local PLGA-CUR vesicles administration, further suggest that PLGA-CUR formulation should be developed as a new potential drug in the treatment of pain in humans. _____________________________________ 1. M. Sinha, L. Gautam, P.K. Shukla et al., Mediators Inflamm., 2013, 258209. 2. M. Musu, G. Finco, R. Antonucci et al., Eur. Rev. Med. Pharmacol. Sci, 2011, 15, 1461. 3. R. Benyamin, A.M. Trescot, S. Datta et al., Pain Physician, 2018, S105. 4. S.C. Gupta, G. Kismali, B.B. Aggarwal, Biofactors, 2013, 39, 2. 5. S. Sharma, S.K. Kulkarni, J.N. Agrewala et al., Eur. J. Pharmacol., 2006, 536, 256. 6. L. Allegri, F. Rosignolo,C. Mio et al., J. Cancer Res. Clin. Oncol. 2018, 144, 285. 7. S. Pieretti, A.P. Ranjan, A. Di Giannuario et al., Colloids Surf B Biointerfaces, 2017, 158, 379

Arqueolab-UBA : Un encuentro con la ciencia participativa

Este proyecto es una iniciativa desarrollada por un grupo de investigadores del Instituto de Arqueología(FFyL-UBA) con el propósito de investigar, conservar y difundir el conocimiento sobre el pasado humano a partir del estudio de los materiales culturales. Como proceso de vinculación entre Ciencia y Sociedad proponemos una nueva modalidad de trabajo a partir de la Visibilización del Pensamiento y de la Ciencia Participativa/Abierta y Ciudadana para recopilar diversas inquietudes y conocimientos sistematizados de parte de los integrantes de la comunidad como potenciales científicos ciudadanos y de nuestro equipo de investigación.Facultad de Informátic

Arqueolab-UBA : Un encuentro con la ciencia participativa

Este proyecto es una iniciativa desarrollada por un grupo de investigadores del Instituto de Arqueología(FFyL-UBA) con el propósito de investigar, conservar y difundir el conocimiento sobre el pasado humano a partir del estudio de los materiales culturales. Como proceso de vinculación entre Ciencia y Sociedad proponemos una nueva modalidad de trabajo a partir de la Visibilización del Pensamiento y de la Ciencia Participativa/Abierta y Ciudadana para recopilar diversas inquietudes y conocimientos sistematizados de parte de los integrantes de la comunidad como potenciales científicos ciudadanos y de nuestro equipo de investigación.Facultad de Informátic