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Background. The involvement of IL-1β and other pro-inflammatory cytokines in most forms of glomerulonephritis is now well established. The P2X7 receptor, an ATP-sensitive P2X receptor, functions not only as a non-selective cation channel, but it is also involved in the rapid processing and release of IL-1β, apoptosis and necrotic cell death. Therefore, we wanted to investigate if expression of this receptor is altered in the glomeruli of rodent models of glomerulonephritis.Methods. P2X7 receptor protein expression was investigated using immunohistochemistry, and apoptosis was assessed using the TUNEL assay and caspase-3 immunostaining. Real-time PCR with gene-specific primers was used to detect P2X7, IL-1β, p53, bax and bcl-2 mRNA expression.Results. Although the levels of the P2X7 receptor protein in mouse kidney are normally very low, or undetectable, we detected an increase in glomerular expression of this receptor and an increase in glomerular apoptotic cells in a mouse model of accelerated nephrotoxic nephritis. We also observed increased glomerular and tubular expression of the P2X7 receptor protein in renal biopsy tissue of patients with autoimmune-related glomerulonephritis. Furthermore, P2X7 receptor mRNA increased in the kidneys of a rat model of proliferative glomerulonephritis and this coincided with the onset of proteinuria. We also observed increased mRNA expression of Il-1β and the pro-apoptotic markers p53 and bax, but not of anti-apoptotic bcl-2.Conclusion. Although there is an association between expression of the pro-inflammatory and pro-apoptotic P2X7 receptor and glomerulonephritis in these rodent models, and in at least one form of human glomerulonephritis, the underlying relationship and its functional significance remain to be explored. [ABSTRACT FROM AUTHOR]

Antecedentes: el glioblastoma (GB) es uno de los tumores más agresivos que afectan al cerebro. Es tratado mediante resección y radioterapia combinada con quimioterapia (temozolomida); no obstante, la supervivencia es de aproximadamente 15 meses, por lo que se requieren nuevas alternativas terapéuticas. Recientemente, en nuestro laboratorio demostramos que el albendazol (ALB), su metabolito sulfóxido de albendazol (ALBSO) y la melatonina (MLT), presentan actividad citotóxica en células de glioma C6, por lo que el objetivo de este trabajo fue evaluar el efecto de combinaciones de ALB-MLT y ALBSO-MLT sobre la misma línea celular. Métodos: células C6 se trataron con las combinaciones siguientes: (I) ALB 0.6µM-MLT 0.6 mM y cuatro diluciones en proporción 1:1; (II) ALB 0.96µM-MLT 0.24 mM y cuatro diluciones en proporción 4:1; (III) ALBSO 20 µM-MLT 1.0 mM y cuatro diluciones en proporción 20:1 y (IV) ALBSO 20.5 µM-MLT 0.5 mM y cuatro diluciones en proporción 20.5:0.5. La viabilidad celular se evaluó con la técnica MTT. El índice de combinación se determinó empleando la metodología de Chou-Talalay y el software CompuSyn. El efecto de las combinaciones sobre la apoptosis se determinó mediante citometría de flujo. Los experimentos se realizaron por cuadruplicado.Núm. de registro del protocolo: 150/16. Resultados: la mayoría de las combinaciones presentaron sinergismo, siendo las más relevantes ALB 0.6µM-MLT 0.6 mM; ALB 0.48µM-MLT 0.12 mM y ALBSO 20µM-MLT1.0 mM. La apoptosis se incrementó significativamente con las combinaciones, en comparación con los fármacos individuales y el control. Conclusiones: las combinaciones ALB-MLT y ALBSOMLT podría ser una estrategia útil para el tratamiento de GB, considerando que estos fármacos son menos tóxicos y costosos que los utilizados actualmente. Se requieren más estudios para conocer los mecanismos de la actividad citotóxica de las combinaciones. [ABSTRACT FROM AUTHOR]

The nearby Sun-like star GJ 758 hosts a cold substellar companion, GJ 758 B, at a projected separation of ≲30 au, previously detected in high-contrast multi-band photometric observations. In order to better constrain the companion’s physical characteristics, we acquired the first low-resolution (R ∼ 50) near-infrared spectrum of it using the high-contrast hyperspectral imaging instrument Project 1640 on Palomar Observatory’s 5 m Hale telescope. We obtained simultaneous images in 32 wavelength channels covering the Y, J, and H bands (∼952–1770 nm), and used data processing techniques based on principal component analysis to efficiently subtract chromatic background speckle-noise. GJ 758 B was detected in four epochs during 2013 and 2014. Basic astrometric measurements confirm its apparent northwest trajectory relative to the primary star, with no clear signs of orbital curvature. Spectra of SpeX/IRTF observed T dwarfs were compared to the combined spectrum of GJ 758 B, with χ2 minimization suggesting a best fit for spectral type T7.0 ± 1.0, but with a shallow minimum over T5–T8. Fitting of synthetic spectra from the BT-Settl13 model atmospheres gives an effective temperature Teff = 741 ± 25 K and surface gravity dex (cgs). Our derived best-fit spectral type and effective temperature from modeling of the low-resolution spectrum suggest a slightly earlier and hotter companion than previous findings from photometric data, but do not rule out current results, and confirm GJ 758 B as one of the coolest sub-stellar companions to a Sun-like star to date. [ABSTRACT FROM AUTHOR]