Ultrasound-Responsive Nrf2-Targeting siRNA-Loaded Nanobubbles for Enhancing the Treatment of Melanoma

The siRNA-mediated inhibition of nuclear factor E2-related factor 2 (Nrf2) can be an attractive approach to overcome chemoresistance in various malignant tumors, including melanoma. This work aims at designing a new type of chitosan-shelled nanobubble for the delivery of siRNA against Nrf2 in combination with an ultrasound. A new preparation method based on a water–oil–water (W/O/W) double-emulsion was purposely developed for siRNA encapsulation in aqueous droplets within a nanobubble core. Stable, very small NB formulations were obtained, with sizes of about 100 nm and a positive surface charge. siRNA was efficiently loaded in NBs, reaching an encapsulation efficiency of about 90%. siNrf2-NBs downregulated the target gene in M14 cells, sensitizing the resistant melanoma cells to the cisplatin treatment. The combination with US favored NB cell uptake and transfection efficiency. Based on the results, nanobubbles have shown to be a promising US responsive tool for siRNA delivery, able to overcome chemoresistance in melanoma cancer cells

Nova forma anatômica de face oclusal em primeiros molares superiores permanent

Introduction: an undefined sulcus on the permanent maxillary first molars (PMFM) allowed the identification of two types of occlusal surfaces: that described by Figún and Garino, Type 1 for the research group, and Type 2, characterized by the presence of a sulcus above the oblique ridge, that runs along it without breaking it. This observation allowed studies to be undertaken in order to determine its presence and investigate its origin, direction and length, to characterize it and register it as a new form of occlusal surface. Methods: we worked with natural PMFM, both inert and in patients, to demonstrate the presence of the sulcus and the PMFM that present the groove in order to characterize it. The method was observational and descriptive. Results: there is a predominance of cases in which the occlusal surface of the PMFM presents a sulcus that partially runs along the oblique ridge, without breaking it. It begins in the main central triangular fossa and runs towards the distal and palatal, its length varying between 1 and 2 mm. These results have allowed this occlusal surface to be registered as Type II PMFM. Conclusion: the PMFM presents two types of occlusal surface: Type I and Type II.Introducción: un surco no tipificado, en los primeros molares superiores permanentes (PMSP), permitió distinguir dos tipos  de cara oclusal: la descrita por Figún y Garino, Tipo I para el grupo de investigación, y Tipo II, caracterizada por la presencia de un  surco sobre la apófisis oblicua, que la discurre sin interrumpirla. Este elemento dio lugar a la realización de estudios con el fin de deter- minar su presencia e investigar origen, dirección y longitud para caracterizarlo y registrarlo como una nueva forma anatómica de cara  oclusal. Métodos: se trabajó con PMSP naturales inertes y de pacientes para evidenciar la presencia del surco y con PMSP que presenten  el surco para caracterizarlo. El método fue observacional y descriptivo. Resultados: existe un predominio de casos en los que la cara  oclusal del PMSP presenta un surco que, sin cortar a la apófisis oblicua, la recorre parcialmente. Se origina en la fosa principal central  triangular. La dirección es hacia distal y palatino y su longitud varía entre 1 y 2 mm. Esto ha permitido registrar esta cara oclusal, como  PMSP Tipo II. Conclusión: el PMSP presenta dos tipos de cara oclusal: Tipo I y Tipo II.DOI: http://dx.doi.org/10.16925/od.v10i18.717Introdução: um sulco não tipificado, nos primeiros molares superiores permanentes (PMSP), permitiu diferenciar dois tipos de face oclusal: a descrita por Figún e Garino, Tipo I para o grupo de pesquisa, e Tipo II, caracterizada pela presença de um sulco sobre a apófise oblíqua, que se estende sem interrupção. Este elemento levou à realização de es-tudos com o objetivo de determinar sua presença e pesquisar a origem, direção e longitude para caracterizá-lo e registrá-lo como uma nova for-ma anatômica de fase oclusal. Métodos: trabalhou-se com PMSP naturais inertes e de pacientes para evidenciar a presença do sulco e PMSP que apresentem o sulco para caracterizá-lo. O método foi observacional e descritivo. Resultados: existe um predomínio de casos em que a face oclu-sal do PMSP apresenta um sulco que, sem cortar a apófise oblíqua, esten-de-se parcialmente por ela. Origina-se na fossa principal central trian-gular. A direção é no sentido distal e palatino e sua longitude varia entre 1 a 2 mm. Isso permitiu registrar essa face oclusal, como PMSP Tipo II. Conclusão: o PMSP apresenta dois tipos de face oclusal: Tipo I e Tipo II

High Prevalence of Hepatitis C Virus Genotype 1b Infection in a Small Town of Argentina. Phylogenetic and Bayesian Coalescent Analysis

Previous studies in Argentina have documented a general prevalence of Hepatitis C Virus (HCV) infection close to 2%. In addition, a high prevalence of HCV has been recently reported in different Argentinean small rural communities. In this work, we performed a study aimed at analyzing the origins and diversification patterns of an HCV outbreak in Wheelwright, a small rural town located in Santa Fe province (Argentina)

Evaluation of the effectiveness of some drugs for the treatment of canine hepatozoonosis

La hepatozoonosis canina es una enfermedad parasitaria, adquirida por la ingestión de garrapatas infectadas con protozoarios del género Hepatozoon (H). Hepatozoon canis y Hepatozoon americanum son las dos especies que pueden infectar al perro. La presentación clínica de la infección con Hepatozoon canis es muy variable, pudiendo ser asintomática o manifestarse con signos de enfermedad leves a severos. Los exámenes hematológicos revelan ligera anemia no regenerativa, marcada leucocitosis neutrofílica con desvío a la izquierda y monocitosis en los casos de hepatozoonosis clínica. El diagnóstico se realiza mediante la visualización mediante el microscopio óptico de los gamontes en neutrófilos y monocitos en frotis de sangre coloreados. No existe, hasta el momento, un tratamiento eficaz para esta parasitosis. El fármaco más utilizado es el dipropionato de imidocarb, aunque con resultados variables. El objetivo de este trabajo fue evaluar tres opciones terapéuticas para la erradicación de Hepatozoon spp. de la sangre de perros infectados. Se utilizaron 18 perros parasitados naturalmente y se evaluaron tres fármacos: dipropionato de imidocarb, toltrazuril y espiramicina. En todos los perros tratados disminuyó el promedio de infección, presentando similares valores medios de leucocitos infectados. El análisis estadístico arrojó una diferencia significativa solo en el tratamiento de la parasitosis con dipropionato de imidocarb. En virtud de los resultados obtenidos con los tratamientos llevados a cabo con los diferentes fármacos, se concluye que ninguno es totalmente efectivo para la desaparición del parásito de la sangre, siendo el dipropionato de imidocarb el de mejor comportamiento.Canine hepatozoonosis is a parasitic disease, acquired by ingestion of ticks infected with protozoa of the genus Hepatozoon (H). Hepatozoon canis and Hepatozoon americanum are the two species that can infect dogs. The clinical presentation of Hepatozoon canis infection is highly variable and may be asymptomatic or show signs of mild to severe disease. In clinical hepatozoonosis, haematological tests reveal slight non regenerative anemia, marked neutrophilic leukocytosis with left shift and monocytosis. Diagnosis is made by the visualization of gamonts in neutrophils and monocytes in stained blood smears using an optical microscope. To date, there is no effective treatment for hepatozoonsis; imidocarb propionate is the most commonly used drug, although results are variable. The aim of this study was to evaluate three therapeutic options for the eradication of Hepatozoon spp. from blood of infected dogs. Three drugs (imidocarb dipropionate, toltrazuril and spiramycin) were evaluated in 18 naturally infected dogs. In all treated dogs the infection averages decreased, showing similar mean values of infected leukocytes. The statistical analysis showed a significant difference only in the treatment of this parasitosis with imidocarb dipropionate. It is concluded that none of the drugs are fully effective in removing the parasite from the blood, but imidocarb dipropionate showed the best results.Facultad de Ciencias Veterinaria

Discovery of novel herpes simplexviruses in wild gorillas, bonobos, and chimpanzees supports zoonotic origin of HSV-2

Viruses closely related to human pathogens can reveal the origins of human infectious diseases. Human herpes simplexvirus type 1 (HSV-1) and type 2 (HSV-2) are hypothesized to have arisen via host-virus codivergence and cross-species transmission. We report the discovery of novel herpes simplexviruses during a large-scale screening of fecal samples from wild gorillas, bonobos, and chimpanzees. Phylogenetic analysis indicates that, contrary to expectation, simplexviruses from these African apes are all more closely related to HSV-2 than to HSV-1. Molecular clock-based hypothesis testing suggests the divergence between HSV-1 and the African great ape simplexviruses likely represents a codivergence event between humans and gorillas. The simplexviruses infecting African great apes subsequently experienced multiple cross-species transmission events over the past 3 My, the most recent of which occurred between humans and bonobos around 1 Ma. These findings revise our understanding of the origins of human herpes simplexviruses and suggest that HSV-2 is one of the earliest zoonotic pathogens

A novel patient-derived tumorgraft model with TRAF1-ALK anaplastic large-cell lymphoma translocation.

Although anaplastic large-cell lymphomas (ALCL) carrying anaplastic lymphoma kinase (ALK) have a relatively good prognosis, aggressive forms exist. We have identified a novel translocation, causing the fusion of the TRAF1 and ALK genes, in one patient who presented with a leukemic ALK+ ALCL (ALCL-11). To uncover the mechanisms leading to high-grade ALCL, we developed a human patient-derived tumorgraft (hPDT) line. Molecular characterization of primary and PDT cells demonstrated the activation of ALK and nuclear factor kB (NFkB) pathways. Genomic studies of ALCL-11 showed the TP53 loss and the in vivo subclonal expansion of lymphoma cells, lacking PRDM1/Blimp1 and carrying c-MYC gene amplification. The treatment with proteasome inhibitors of TRAF1-ALK cells led to the downregulation of p50/p52 and lymphoma growth inhibition. Moreover, a NFkB gene set classifier stratified ALCL in distinct subsets with different clinical outcome. Although a selective ALK inhibitor (CEP28122) resulted in a significant clinical response of hPDT mice, nevertheless the disease could not be eradicated. These data indicate that the activation of NFkB signaling contributes to the neoplastic phenotype of TRAF1-ALK ALCL. ALCL hPDTs are invaluable tools to validate the role of druggable molecules, predict therapeutic responses and implement patient specific therapies

Novelty Response of Wild African Apes to Camera Traps

Temperament and personality research in humans and nonhuman animals measures behavioral variation in individual, population, or species-specific traits with implications for survival and fitness, such as social status, foraging and mating success [1–5]. Curiosity and risk-taking tendencies have been studied extensively across taxa by measuring boldness and exploration responses to experimental novelty exposure [3,4,6–15]. Here, we conduct a natural field experiment using wildlife monitoring technology to test variation in the reaction of wild great apes (43 groups of naïve chimpanzees, bonobos and western gorillas, across 14 field sites in Africa) to a novel object, the camera-trap. Bonobo and gorilla groups demonstrated a stronger looking impulse towards the camera-trap device compared to chimpanzees, suggesting higher visual attention and curiosity. Bonobos were also more likely to show alarm and other fearful behaviors, although such neophobic (and conversely, neophilic) responses were generally rare. Among all three species, individuals looked at cameras longer when they were young, were associating with fewer individuals, and did not live near a long-term research site. Overall, these findings partially validate results from great ape novelty paradigms in captivity [7,8]. We further suggest that species-typical leadership styles [16] and social and environmental effects, including familiarity with humans, best explain novelty responses of wild great apes. In sum, this study illustrates the feasibility of large-scale field experiments and the importance of both intrinsic and extrinsic factors in shaping animal curiosity